Bio

Academic Appointments


Research & Scholarship

Current Research and Scholarly Interests


Human genetic and cultural evolution, mathematical biology, demography of China

Teaching

2013-14 Courses


Graduate and Fellowship Programs


  • Biology (School of Humanities and Sciences) (Phd Program)

Publications

Journal Articles


  • The role of cultural transmission in human demographic change: An age-structured model. Theoretical population biology Fogarty, L., Creanza, N., Feldman, M. W. 2013; 88: 68-77

    Abstract

    Human populations vary demographically with population sizes ranging from small groups of hunter-gatherers with less than fifty individuals to vast cities containing many millions. Here we investigate how the cultural transmission of traits affecting survival, fertility, or both can influence the birth rate, age structure, and asymptotic growth rate of a population. We show that the strong spread of such a trait can lead to a demographic transition, similar to that experienced in Europe in the late 19th and early 20th centuries, without using ecological or economic optimizing models. We also show that the spread of a cultural trait that increases fertility, but not survival, can cause demographic change similar to the 'Neolithic demographic transition': a period of increased population growth that is thought to have accompanied the transition from hunter-gatherer to agricultural lifestyles. We investigate the roles of vertical, oblique, and horizontal learning of such a trait in this transition and find that compared to vertical learning alone, horizontal and oblique learning can accelerate the trait's spread, lead to faster population growth, and increase its equilibrium frequency.

    View details for DOI 10.1016/j.tpb.2013.06.006

    View details for PubMedID 23867394

  • Evolution with stochastic fitnesses: A role for recombination. Theoretical population biology Carja, O., Liberman, U., Feldman, M. W. 2013; 86: 29-42

    Abstract

    Phenotypic adaptation to fluctuating environments has been an important focus in the population genetic literature. Previous studies have shown that evolution under temporal variation is determined not only by expected fitness in a given generation, but also by the degree of variation in fitness over generations; in an uncertain environment, alleles that increase the geometric mean fitness can invade a randomly mating population at equilibrium. This geometric mean principle governs the evolutionary interplay of genes controlling mean phenotype and genes controlling phenotypic variation, such as genetic regulators of the epigenetic machinery. Thus, it establishes an important role for stochastic epigenetic variation in adaptation to fluctuating environments: by modifying the geometric mean fitness, variance-modifying genes can change the course of evolution and determine the long-term trajectory of the evolving system. The role of phenotypic variance has previously been studied in systems in which the only driving force is natural selection, and there is no recombination between mean- and variance-modifying genes. Here, we develop a population genetic model to investigate the effect of recombination between mean- and variance-modifiers of phenotype on the geometric mean principle under different environmental regimes and fitness landscapes. We show that interactions of recombination with stochastic epigenetic variation and environmental fluctuations can give rise to complex evolutionary dynamics that differ from those in systems with no recombination.

    View details for DOI 10.1016/j.tpb.2013.02.005

    View details for PubMedID 23517905

  • Long-term evolution is surprisingly predictable in lattice proteins JOURNAL OF THE ROYAL SOCIETY INTERFACE Palmer, M. E., Moudgil, A., Feldman, M. W. 2013; 10 (82)

    Abstract

    It has long been debated whether natural selection acts primarily upon individual organisms, or whether it also commonly acts upon higher-level entities such as lineages. Two arguments against the effectiveness of long-term selection on lineages have been (i) that long-term evolutionary outcomes will not be sufficiently predictable to support a meaningful long-term fitness and (ii) that short-term selection on organisms will almost always overpower long-term selection. Here, we use a computational model of protein folding and binding called 'lattice proteins'. We quantify the long-term evolutionary success of lineages with two metrics called the k-fitness and k-survivability. We show that long-term outcomes are surprisingly predictable in this model: only a small fraction of the possible outcomes are ever realized in multiple replicates. Furthermore, the long-term fitness of a lineage depends only partly on its short-term fitness; other factors are also important, including the 'evolvability' of a lineage-its capacity to produce adaptive variation. In a system with a distinct short-term and long-term fitness, evolution need not be 'short-sighted': lineages may be selected for their long-term properties, sometimes in opposition to short-term selection. Similar evolutionary basins of attraction have been observed in vivo, suggesting that natural biological lineages will also have a predictive long-term fitness.

    View details for DOI 10.1098/rsif.2013.0026

    View details for Web of Science ID 000316415600015

    View details for PubMedID 23466559

  • The coevolution of long-term pair bonds and cooperation. Journal of evolutionary biology Song, Z., Feldman, M. W. 2013; 26 (5): 963-970

    Abstract

    The evolution of social traits may not only depend on but also change the social structure of the population. In particular, the evolution of pairwise cooperation, such as biparental care, depends on the pair-matching distribution of the population, and the latter often emerges as a collective outcome of individual pair-bonding traits, which are also under selection. Here, we develop an analytical model and individual-based simulations to study the coevolution of long-term pair bonds and cooperation in parental care, where partners play a Snowdrift game in each breeding season. We illustrate that long-term pair bonds may coevolve with cooperation when bonding cost is below a threshold. As long-term pair bonds lead to assortative interactions through pair-matching dynamics, they may promote the prevalence of cooperation. In addition to the pay-off matrix of a single game, the evolutionarily stable equilibrium also depends on bonding cost and accidental divorce rate, and it is determined by a form of balancing selection because the benefit from pair-bond maintenance diminishes as the frequency of cooperators increases. Our findings highlight the importance of ecological factors affecting social bonding cost and stability in understanding the coevolution of social behaviour and social structures, which may lead to the diversity of biological social systems.

    View details for DOI 10.1111/jeb.12111

    View details for PubMedID 23496797

  • Plant-animal mutualism in biological markets: Evolutionary and ecological dynamics driven by non-heritable phenotypic variance. Theoretical population biology Song, Z., Feldman, M. W. 2013; 88C: 20-30

    Abstract

    Mutualism between plants and animals, such as in pollination and seed dispersal, is a fundamental mechanism facilitating the productivity and biodiversity of ecosystems, and it is often considered as an analog of a free-market economy. The coevolution of plant reward and animal choosiness, however, involves an apparent paradox due to incomplete information and limited mutation rates: plant rewards evolve only when animals are choosy, but choosy animals purge the heritable variations of plants, which then favors less choosy animals. Here we use a two-species mathematical model to illustrate how non-heritable phenotypic variances of plants may facilitate the coevolution of rewards and choosiness and solve the paradox with low mutation rates. We simultaneously track the ecological and evolutionary dynamics and show that the population ratio links the two processes and tunes the stable eco-evolutionary equilibrium. Numerical simulations confirm the analytic prediction with varying mutation rates (heritable variance). The efficiency of a biological market is generally suboptimal due to the information constraint and individual competition.

    View details for PubMedID 23791699

  • A Tale of Two Haplotypes: The EDA2R/AR Intergenic Region Is the Most Divergent Genomic Segment between Africans and East Asians in the Human Genome HUMAN BIOLOGY Casto, A. M., Henn, B. M., Kidd, J. M., Bustamante, C. D., Feldman, M. W. 2012; 84 (6): 641-694

    Abstract

    Single nucleotide polymorphisms (SNPs) with large allele frequency differences between human populations are relatively rare. The longest run of SNPs with an allele frequency difference of one between the Yoruba of Nigeria and the Han Chinese is found on the long arm of the X chromosome in the intergenic region separating the EDA2R and AR genes. It has been proposed that the unusual allele frequency distributions of these SNPs are the result of a selective sweep affecting African populations that occurred after the out-of-Africa migration. To investigate the evolutionary history of the EDA2R/AR intergenic region, we characterized the haplotype structure of 52 of its highly differentiated SNPs. Using a publicly available data set of 3,000 X chromosomes from 65 human populations, we found that nearly all human X chromosomes carry one of two modal haplotypes for these 52 SNPs. The predominance of two highly divergent haplotypes at this locus was confirmed by use of a subset of individuals sequenced to high coverage. The first of these haplotypes, the α-haplotype is at high frequencies in most of the African populations surveyed and likely arose before the separation of African populations into distinct genetic entities. The second, the β-haplotype, is frequent or fixed in all non-African populations and likely arose in East Africa before the out-of-Africa migration. We also observed a small group or rare haplotypes with no clear relationship to the α- and β-haplotypes. These haplotypes occur at relatively high frequencies in African hunter-gatherer populations, such as the San and Mbuti Pygmies. Our analysis indicates that these haplotypes are part of a pool of diverse, ancestral haplotypes that have now been almost entirely replaced by the α- and β-haplotypes. We suggest that the rise of the α- and β-haplotypes was the result of the demographic forces that human populations experienced during the formation of modern African populations and the out-of-Africa migration. However, we also present evidence that this region is the target of selection in the form of positive selection on the α- and β-haplotypes and of purifying the selection against α/β recombinants.

    View details for Web of Science ID 000322906700002

    View details for PubMedID 23959643

  • Limited Evidence for Classic Selective Sweeps in African Populations GENETICS Granka, J. M., Henn, B. M., Gignoux, C. R., Kidd, J. M., Bustamante, C. D., Feldman, M. W. 2012; 192 (3): 1049-?

    Abstract

    While hundreds of loci have been identified as reflecting strong-positive selection in human populations, connections between candidate loci and specific selective pressures often remain obscure. This study investigates broader patterns of selection in African populations, which are underrepresented despite their potential to offer key insights into human adaptation. We scan for hard selective sweeps using several haplotype and allele-frequency statistics with a data set of nearly 500,000 genome-wide single-nucleotide polymorphisms in 12 highly diverged African populations that span a range of environments and subsistence strategies. We find that positive selection does not appear to be a strong determinant of allele-frequency differentiation among these African populations. Haplotype statistics do identify putatively selected regions that are shared across African populations. However, as assessed by extensive simulations, patterns of haplotype sharing between African populations follow neutral expectations and suggest that tails of the empirical distributions contain false-positive signals. After highlighting several genomic regions where positive selection can be inferred with higher confidence, we use a novel method to identify biological functions enriched among populations' empirical tail genomic windows, such as immune response in agricultural groups. In general, however, it seems that current methods for selection scans are poorly suited to populations that, like the African populations in this study, are affected by ascertainment bias and have low levels of linkage disequilibrium, possibly old selective sweeps, and potentially reduced phasing accuracy. Additionally, population history can confound the interpretation of selection statistics, suggesting that greater care is needed in attributing broad genetic patterns to human adaptation.

    View details for DOI 10.1534/genetics.112.144071

    View details for Web of Science ID 000310793900019

    View details for PubMedID 22960214

  • The great human expansion PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Henn, B. M., Cavalli-Sforza, L. L., Feldman, M. W. 2012; 109 (44): 17758-17764

    Abstract

    Genetic and paleoanthropological evidence is in accord that today's human population is the result of a great demic (demographic and geographic) expansion that began approximately 45,000 to 60,000 y ago in Africa and rapidly resulted in human occupation of almost all of the Earth's habitable regions. Genomic data from contemporary humans suggest that this expansion was accompanied by a continuous loss of genetic diversity, a result of what is called the "serial founder effect." In addition to genomic data, the serial founder effect model is now supported by the genetics of human parasites, morphology, and linguistics. This particular population history gave rise to the two defining features of genetic variation in humans: genomes from the substructured populations of Africa retain an exceptional number of unique variants, and there is a dramatic reduction in genetic diversity within populations living outside of Africa. These two patterns are relevant for medical genetic studies mapping genotypes to phenotypes and for inferring the power of natural selection in human history. It should be appreciated that the initial expansion and subsequent serial founder effect were determined by demographic and sociocultural factors associated with hunter-gatherer populations. How do we reconcile this major demic expansion with the population stability that followed for thousands years until the inventions of agriculture? We review advances in understanding the genetic diversity within Africa and the great human expansion out of Africa and offer hypotheses that can help to establish a more synthetic view of modern human evolution.

    View details for DOI 10.1073/pnas.1212380109

    View details for Web of Science ID 000311149900021

    View details for PubMedID 23077256

  • Models of Cultural Niche Construction with Selection and Assortative Mating PLOS ONE Creanza, N., Fogarty, L., Feldman, M. W. 2012; 7 (8)

    Abstract

    Niche construction is a process through which organisms modify their environment and, as a result, alter the selection pressures on themselves and other species. In cultural niche construction, one or more cultural traits can influence the evolution of other cultural or biological traits by affecting the social environment in which the latter traits may evolve. Cultural niche construction may include either gene-culture or culture-culture interactions. Here we develop a model of this process and suggest some applications of this model. We examine the interactions between cultural transmission, selection, and assorting, paying particular attention to the complexities that arise when selection and assorting are both present, in which case stable polymorphisms of all cultural phenotypes are possible. We compare our model to a recent model for the joint evolution of religion and fertility and discuss other potential applications of cultural niche construction theory, including the evolution and maintenance of large-scale human conflict and the relationship between sex ratio bias and marriage customs. The evolutionary framework we introduce begins to address complexities that arise in the quantitative analysis of multiple interacting cultural traits.

    View details for DOI 10.1371/journal.pone.0042744

    View details for Web of Science ID 000307500800020

    View details for PubMedID 22905167

  • Genomic Patterns of Homozygosity in Worldwide Human Populations AMERICAN JOURNAL OF HUMAN GENETICS Pemberton, T. J., Absher, D., Feldman, M. W., Myers, R. M., Rosenberg, N. A., Li, J. Z. 2012; 91 (2): 275-292

    Abstract

    Genome-wide patterns of homozygosity runs and their variation across individuals provide a valuable and often untapped resource for studying human genetic diversity and evolutionary history. Using genotype data at 577,489 autosomal SNPs, we employed a likelihood-based approach to identify runs of homozygosity (ROH) in 1,839 individuals representing 64 worldwide populations, classifying them by length into three classes-short, intermediate, and long-with a model-based clustering algorithm. For each class, the number and total length of ROH per individual show considerable variation across individuals and populations. The total lengths of short and intermediate ROH per individual increase with the distance of a population from East Africa, in agreement with similar patterns previously observed for locus-wise homozygosity and linkage disequilibrium. By contrast, total lengths of long ROH show large interindividual variations that probably reflect recent inbreeding patterns, with higher values occurring more often in populations with known high frequencies of consanguineous unions. Across the genome, distributions of ROH are not uniform, and they have distinctive continental patterns. ROH frequencies across the genome are correlated with local genomic variables such as recombination rate, as well as with signals of recent positive selection. In addition, long ROH are more frequent in genomic regions harboring genes associated with autosomal-dominant diseases than in regions not implicated in Mendelian diseases. These results provide insight into the way in which homozygosity patterns are produced, and they generate baseline homozygosity patterns that can be used to aid homozygosity mapping of genes associated with recessive diseases.

    View details for DOI 10.1016/j.ajhg.2012.06.014

    View details for Web of Science ID 000307608700006

    View details for PubMedID 22883143

  • Survivability Is More Fundamental Than Evolvability PLOS ONE Palmer, M. E., Feldman, M. W. 2012; 7 (6)

    Abstract

    For a lineage to survive over long time periods, it must sometimes change. This has given rise to the term evolvability, meaning the tendency to produce adaptive variation. One lineage may be superior to another in terms of its current standing variation, or it may tend to produce more adaptive variation. However, evolutionary outcomes depend on more than standing variation and produced adaptive variation: deleterious variation also matters. Evolvability, as most commonly interpreted, is not predictive of evolutionary outcomes. Here, we define a predictive measure of the evolutionary success of a lineage that we call the k-survivability, defined as the probability that the lineage avoids extinction for k generations. We estimate the k-survivability using multiple experimental replicates. Because we measure evolutionary outcomes, the initial standing variation, the full spectrum of generated variation, and the heritability of that variation are all incorporated. Survivability also accounts for the decreased joint likelihood of extinction of sub-lineages when they 1) disperse in space, or 2) diversify in lifestyle. We illustrate measurement of survivability with in silico models, and suggest that it may also be measured in vivo using multiple longitudinal replicates. The k-survivability is a metric that enables the quantitative study of, for example, the evolution of 1) mutation rates, 2) dispersal mechanisms, 3) the genotype-phenotype map, and 4) sexual reproduction, in temporally and spatially fluctuating environments. Although these disparate phenomena evolve by well-understood microevolutionary rules, they are also subject to the macroevolutionary constraint of long-term survivability.

    View details for DOI 10.1371/journal.pone.0038025

    View details for Web of Science ID 000305583300018

    View details for PubMedID 22723844

  • Most Networks in Wagner's Model Are Cycling PLOS ONE Pinho, R., Borenstein, E., Feldman, M. W. 2012; 7 (4)

    Abstract

    In this paper we study a model of gene networks introduced by Andreas Wagner in the 1990s that has been used extensively to study the evolution of mutational robustness. We investigate a range of model features and parameters and evaluate the extent to which they influence the probability that a random gene network will produce a fixed point steady state expression pattern. There are many different types of models used in the literature, (discrete/continuous, sparse/dense, small/large network) and we attempt to put some order into this diversity, motivated by the fact that many properties are qualitatively the same in all the models. Our main result is that random networks in all models give rise to cyclic behavior more often than fixed points. And although periodic orbits seem to dominate network dynamics, they are usually considered unstable and not allowed to survive in previous evolutionary studies. Defining stability as the probability of fixed points, we show that the stability distribution of these networks is highly robust to changes in its parameters. We also find sparser networks to be more stable, which may help to explain why they seem to be favored by evolution. We have unified several disconnected previous studies of this class of models under the framework of stability, in a way that had not been systematically explored before.

    View details for DOI 10.1371/journal.pone.0034285

    View details for Web of Science ID 000305338600021

    View details for PubMedID 22511935

  • An equilibrium for phenotypic variance in fluctuating environments owing to epigenetics JOURNAL OF THE ROYAL SOCIETY INTERFACE Carja, O., Feldman, M. W. 2012; 9 (69): 613-623

    Abstract

    The connection between random environments and genetic and phenotypic variability has been a major focus in the population genetic literature. By providing differential access to the underlying genetic information, epigenetic variation could play an important role in the interaction between environmental and phenotypic variation. Using simulation, we model epigenetic plasticity during development by investigating the dynamics of genetic regulators of the epigenetic machinery that change the variance of the phenotype, while having no effect on the phenotype's mean. Previous studies have found that increased phenotypic variance is selected for if the environment is fluctuating. Here, we find that when a variance-increasing allele achieves a sufficiently high frequency, it can be out-competed by a variance-reducing allele, with the consequence that the population evolves to an equilibrium phenotypic variability. This equilibrium is shown to be robust to different initial conditions, but to depend heavily on parameters of the model, such as the mutation rate, the fitness landscape and the nature of the environmental fluctuation. Indeed, if there is no mutation at the genes controlling the variance of the phenotype, reduction of this variance is favoured.

    View details for DOI 10.1098/rsif.2011.0390

    View details for Web of Science ID 000300726700002

    View details for PubMedID 21849387

  • Environment-Sensitive Epigenetics and the Heritability of Complex Diseases GENETICS Furrow, R. E., Christiansen, F. B., Feldman, M. W. 2011; 189 (4): 1377-?

    Abstract

    Genome-wide association studies have thus far failed to explain the observed heritability of complex human diseases. This is referred to as the "missing heritability" problem. However, these analyses have usually neglected to consider a role for epigenetic variation, which has been associated with many human diseases. We extend models of epigenetic inheritance to investigate whether environment-sensitive epigenetic modifications of DNA might explain observed patterns of familial aggregation. We find that variation in epigenetic state and environmental state can result in highly heritable phenotypes through a combination of epigenetic and environmental inheritance. These two inheritance processes together can produce familial covariances significantly higher than those predicted by models of purely epigenetic inheritance and similar to those expected from genetic effects. The results suggest that epigenetic variation, inherited both directly and through shared environmental effects, may make a key contribution to the missing heritability.

    View details for DOI 10.1534/genetics.111.131912

    View details for Web of Science ID 000298412100020

    View details for PubMedID 21968193

  • The Spread of Inequality PLOS ONE Rogers, D. S., Deshpande, O., Feldman, M. W. 2011; 6 (9)

    Abstract

    The causes of socioeconomic inequality have been debated since the time of Plato. Many reasons for the development of stratification have been proposed, from the need for hierarchical control over large-scale irrigation systems to the accumulation of small differences in wealth over time via inheritance processes. However, none of these explains how unequal societies came to completely displace egalitarian cultural norms over time. Our study models demographic consequences associated with the unequal distribution of resources in stratified societies. Agent-based simulation results show that in constant environments, unequal access to resources can be demographically destabilizing, resulting in the outward migration and spread of such societies even when population size is relatively small. In variable environments, stratified societies spread more and are also better able to survive resource shortages by sequestering mortality in the lower classes. The predictions of our simulation are provided modest support by a range of existing empirical studies. In short, the fact that stratified societies today vastly outnumber egalitarian societies may not be due to the transformation of egalitarian norms and structures, but may instead reflect the more rapid migration of stratified societies and consequent conquest or displacement of egalitarian societies over time.

    View details for DOI 10.1371/journal.pone.0024683

    View details for Web of Science ID 000295262100016

    View details for PubMedID 21957457

  • SPATIAL ENVIRONMENTAL VARIATION CAN SELECT FOR EVOLVABILITY EVOLUTION Palmer, M. E., Feldman, M. W. 2011; 65 (8): 2345-2356

    Abstract

    Previous studies have shown that temporally fluctuating environments can create indirect selection for modifiers of evolvability. Here, we use a simple computational model to investigate whether spatially varying environments (multiple demes with limited migration among them, and a different, static selective optimum in each) can also create indirect selection for increased evolvability. The answer is surprisingly complicated. Spatial variation in the environment can sharply reduce the survival rate of migrants, because migrants may be maladapted to their new deme, relative to incumbents. The incumbent advantage can be removed by occasional extinctions in single demes. After all incumbents in a particular deme die, incoming migrants from other demes will, on average, be similarly maladapted to the new environment. This sets off a race to adapt rapidly. Over many extinction events, and the subsequent invasions by maladapted immigrants into a new environment, indirect selection for the ability to adapt rapidly, also known as high evolvability, may result.

    View details for DOI 10.1111/j.1558-5646.2011.01283.x

    View details for Web of Science ID 000293182700017

    View details for PubMedID 21790580

  • Dispersal of Mycobacterium tuberculosis via the Canadian fur trade PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Pepperell, C. S., Granka, J. M., Alexander, D. C., Behr, M. A., Chui, L., Gordon, J., Guthrie, J. L., Jamieson, F. B., Langlois-Klassen, D., Long, R., Nguyen, D., Wobeser, W., Feldman, M. W. 2011; 108 (16): 6526-6531

    Abstract

    Patterns of gene flow can have marked effects on the evolution of populations. To better understand the migration dynamics of Mycobacterium tuberculosis, we studied genetic data from European M. tuberculosis lineages currently circulating in Aboriginal and French Canadian communities. A single M. tuberculosis lineage, characterized by the DS6(Quebec) genomic deletion, is at highest frequency among Aboriginal populations in Ontario, Saskatchewan, and Alberta; this bacterial lineage is also dominant among tuberculosis (TB) cases in French Canadians resident in Quebec. Substantial contact between these human populations is limited to a specific historical era (1710-1870), during which individuals from these populations met to barter furs. Statistical analyses of extant M. tuberculosis minisatellite data are consistent with Quebec as a source population for M. tuberculosis gene flow into Aboriginal populations during the fur trade era. Historical and genetic analyses suggest that tiny M. tuberculosis populations persisted for ?100 y among indigenous populations and subsequently expanded in the late 19th century after environmental changes favoring the pathogen. Our study suggests that spread of TB can occur by two asynchronous processes: (i) dispersal of M. tuberculosis by minimal numbers of human migrants, during which small pathogen populations are sustained by ongoing migration and slow disease dynamics, and (ii) expansion of the M. tuberculosis population facilitated by shifts in host ecology. If generalizable, these migration dynamics can help explain the low DNA sequence diversity observed among isolates of M. tuberculosis and the difficulties in global elimination of tuberculosis, as small, widely dispersed pathogen populations are difficult both to detect and to eradicate.

    View details for DOI 10.1073/pnas.1016708108

    View details for Web of Science ID 000289680400042

    View details for PubMedID 21464295

  • Hunter-gatherer genomic diversity suggests a southern African origin for modern humans PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Henn, B. M., Gignoux, C. R., Jobin, M., Granka, J. M., Macpherson, J. M., Kidd, J. M., Rodriguez-Botigue, L., Ramachandran, S., Hon, L., Brisbin, A., Lin, A. A., Underhill, P. A., Comas, D., Kidd, K. K., Norman, P. J., Parham, P., Bustamante, C. D., Mountain, J. L., Feldman, M. W. 2011; 108 (13): 5154-5162

    Abstract

    Africa is inferred to be the continent of origin for all modern human populations, but the details of human prehistory and evolution in Africa remain largely obscure owing to the complex histories of hundreds of distinct populations. We present data for more than 580,000 SNPs for several hunter-gatherer populations: the Hadza and Sandawe of Tanzania, and the ?Khomani Bushmen of South Africa, including speakers of the nearly extinct N|u language. We find that African hunter-gatherer populations today remain highly differentiated, encompassing major components of variation that are not found in other African populations. Hunter-gatherer populations also tend to have the lowest levels of genome-wide linkage disequilibrium among 27 African populations. We analyzed geographic patterns of linkage disequilibrium and population differentiation, as measured by F(ST), in Africa. The observed patterns are consistent with an origin of modern humans in southern Africa rather than eastern Africa, as is generally assumed. Additionally, genetic variation in African hunter-gatherer populations has been significantly affected by interaction with farmers and herders over the past 5,000 y, through both severe population bottlenecks and sex-biased migration. However, African hunter-gatherer populations continue to maintain the highest levels of genetic diversity in the world.

    View details for DOI 10.1073/pnas.1017511108

    View details for Web of Science ID 000288894800009

    View details for PubMedID 21383195

  • The influence of social niche on cultural niche construction: modelling changes in belief about marriage form in Taiwan PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Lipatov, M., Brown, M. J., Feldman, M. W. 2011; 366 (1566): 901-917

    Abstract

    With introduction of social niche effects into a model of cultural change, the frequency of a practice cannot predict the frequency of its underlying belief. The combination of a general model with empirical data from a specific case illustrates the importance of collaboration between modellers and field researchers, and identifies the type of quantitative data necessary for analysing case studies. Demographic data from colonial-period household registers in Taiwan document a shift in marriage form within 40 years, from a mixture of uxorilocal marriages and virilocal marriages to the latter's dominance. Ethnographic data indicate marriage-related beliefs, costs, ethnic effects and colonial policies as well as the importance of horizontal cultural transmission. We present a formal model for the effects of moral beliefs about marriage and a population economic index on the decline of uxorilocal marriage. We integrate empirical marriage rates and an estimated economic index to produce five projections of the historical frequencies of one belief. These projections demonstrate how economic development may affect a cultural niche. They also indicate the need for future research on the relationship between wealth and cultural variability, the motivational force of cultural versus social factors, and the process of cultural niche construction.

    View details for DOI 10.1098/rstb.2010.0303

    View details for Web of Science ID 000287302400011

    View details for PubMedID 21320903

  • Genome-Wide Association Study SNPs in the Human Genome Diversity Project Populations: Does Selection Affect Unlinked SNPs with Shared Trait Associations? PLOS GENETICS Casto, A. M., Feldman, M. W. 2011; 7 (1)

    Abstract

    Genome-wide association studies (GWAS) have identified more than 2,000 trait-SNP associations, and the number continues to increase. GWAS have focused on traits with potential consequences for human fitness, including many immunological, metabolic, cardiovascular, and behavioral phenotypes. Given the polygenic nature of complex traits, selection may exert its influence on them by altering allele frequencies at many associated loci, a possibility which has yet to be explored empirically. Here we use 38 different measures of allele frequency variation and 8 iHS scores to characterize over 1,300 GWAS SNPs in 53 globally distributed human populations. We apply these same techniques to evaluate SNPs grouped by trait association. We find that groups of SNPs associated with pigmentation, blood pressure, infectious disease, and autoimmune disease traits exhibit unusual allele frequency patterns and elevated iHS scores in certain geographical locations. We also find that GWAS SNPs have generally elevated scores for measures of allele frequency variation and for iHS in Eurasia and East Asia. Overall, we believe that our results provide evidence for selection on several complex traits that has caused changes in allele frequencies and/or elevated iHS scores at a number of associated loci. Since GWAS SNPs collectively exhibit elevated allele frequency measures and iHS scores, selection on complex traits may be quite widespread. Our findings are most consistent with this selection being either positive or negative, although the relative contributions of the two are difficult to discern. Our results also suggest that trait-SNP associations identified in Eurasian samples may not be present in Africa, Oceania, and the Americas, possibly due to differences in linkage disequilibrium patterns. This observation suggests that non-Eurasian and non-East Asian sample populations should be included in future GWAS.

    View details for DOI 10.1371/journal.pgen.1001266

    View details for Web of Science ID 000286653500005

    View details for PubMedID 21253569

  • A high-resolution human contact network for infectious disease transmission PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Salathe, M., Kazandjieva, M., Lee, J. W., Levis, P., Feldman, M. W., Jones, J. H. 2010; 107 (51): 22020-22025

    Abstract

    The most frequent infectious diseases in humans--and those with the highest potential for rapid pandemic spread--are usually transmitted via droplets during close proximity interactions (CPIs). Despite the importance of this transmission route, very little is known about the dynamic patterns of CPIs. Using wireless sensor network technology, we obtained high-resolution data of CPIs during a typical day at an American high school, permitting the reconstruction of the social network relevant for infectious disease transmission. At 94% coverage, we collected 762,868 CPIs at a maximal distance of 3 m among 788 individuals. The data revealed a high-density network with typical small-world properties and a relatively homogeneous distribution of both interaction time and interaction partners among subjects. Computer simulations of the spread of an influenza-like disease on the weighted contact graph are in good agreement with absentee data during the most recent influenza season. Analysis of targeted immunization strategies suggested that contact network data are required to design strategies that are significantly more effective than random immunization. Immunization strategies based on contact network data were most effective at high vaccination coverage.

    View details for DOI 10.1073/pnas.1009094108

    View details for Web of Science ID 000285521800019

    View details for PubMedID 21149721

  • How Demography, Life History, and Kinship Shape the Evolution of Genomic Imprinting AMERICAN NATURALIST Van Cleve, J., Feldman, M. W., Lehmann, L. 2010; 176 (4): 440-455

    Abstract

    How phenomena like helping, dispersal, or the sex ratio evolve depends critically on demographic and life-history factors. One phenotype that is of particular interest to biologists is genomic imprinting, which results in parent-of-origin-specific gene expression and thus deviates from the predictions of Mendel's rules. The most prominent explanation for the evolution of genomic imprinting, the kinship theory, originally specified that multiple paternity can cause the evolution of imprinting when offspring affect maternal resource provisioning. Most models of the kinship theory do not detail how population subdivision, demography, and life history affect the evolution of imprinting. In this work, we embed the classic kinship theory within an island model of population structure and allow for diverse demographic and life-history features to affect the direction of selection on imprinting. We find that population structure does not change how multiple paternity affects the evolution of imprinting under the classic kinship theory. However, if the degree of multiple paternity is not too large, we find that sex-specific migration and survival and generation overlap are the primary factors determining which allele is silenced. This indicates that imprinting can evolve purely as a result of sex-related asymmetries in the demographic structure or life history of a species.

    View details for DOI 10.1086/656277

    View details for Web of Science ID 000282001800006

    View details for PubMedID 20738206

  • On the Classification of Epistatic Interactions GENETICS Gao, H., Granka, J. M., Feldman, M. W. 2010; 184 (3): 827-U351

    Abstract

    Modern genomewide association studies are characterized by the problem of "missing heritability." Epistasis, or genetic interaction, has been suggested as a possible explanation for the relatively small contribution of single significant associations to the fraction of variance explained. Of particular concern to investigators of genetic interactions is how to best represent and define epistasis. Previous studies have found that the use of different quantitative definitions for genetic interaction can lead to different conclusions when constructing genetic interaction networks and when addressing evolutionary questions. We suggest that instead, multiple representations of epistasis, or epistatic "subtypes," may be valid within a given system. Selecting among these epistatic subtypes may provide additional insight into the biological and functional relationships among pairs of genes. In this study, we propose maximum-likelihood and model selection methods in a hypothesis-testing framework to choose epistatic subtypes that best represent functional relationships for pairs of genes on the basis of fitness data from both single and double mutants in haploid systems. We gauge the performance of our method with extensive simulations under various interaction scenarios. Our approach performs reasonably well in detecting the most likely epistatic subtype for pairs of genes, as well as in reducing bias when estimating the epistatic parameter (epsilon). We apply our approach to two available data sets from yeast (Saccharomyces cerevisiae) and demonstrate through overlap of our identified epistatic pairs with experimentally verified interactions and functional links that our results are likely of biological significance in understanding interaction mechanisms. We anticipate that our method will improve detection of epistatic interactions and will help to unravel the mysteries of complex biological systems.

    View details for DOI 10.1534/genetics.109.111120

    View details for Web of Science ID 000281886300019

    View details for PubMedID 20026678

  • Bacterial Genetic Signatures of Human Social Phenomena among M-tuberculosis from an Aboriginal Canadian Population MOLECULAR BIOLOGY AND EVOLUTION Pepperell, C., Hoeppner, V. H., Lipatov, M., Wobeser, W., Schoolnik, G. K., Feldman, M. W. 2010; 27 (2): 427-440

    Abstract

    Despite a widespread global distribution and highly variable disease phenotype, there is little DNA sequence diversity among isolates of Mycobacterium tuberculosis. In addition, many regional population genetic surveys have revealed a stereotypical structure in which a single clone, lineage, or clade makes up the majority of the population. It is often assumed that dominant clones are highly adapted, that is, the overall structure of M. tuberculosis populations is the result of positive selection. In order to test this assumption, we analyzed genetic data from extant populations of bacteria circulating in Aboriginal communities in Saskatchewan, Canada. Demographic parameters of the bacterial population were estimated from archival epidemiological data collected over approximately 130 years since the onset of epidemic tuberculosis in the host communities. Bacterial genetic data were tested against neutral theory expectations and the local evolutionary history of M. tuberculosis investigated by phylogenetic analysis. Our findings are not consistent with positive selection on the bacterial population. Instead, we uncovered founder effects persisting over decades and barriers to gene flow within the bacterial population. Simulation experiments suggested that a combination of these neutral influences could result in the stereotypical structure of M. tuberculosis populations. Some aspects of population structure were suggestive of background selection, and data were on the whole consistent with combined effects of population bottlenecks, subdivision, and background selection. Neutral phenomena, namely, bottlenecks and partitions within populations, are prominent influences on the evolution of M. tuberculosis and likely contribute to restricted genetic diversity observed within this species. Given these influences, a complex evolutionary model will be required to define the relative fitness of different M. tuberculosis lineages and, ultimately, to uncover the genetic basis for its success as a pathogen.

    View details for DOI 10.1093/molbev/msp261

    View details for Web of Science ID 000273704400020

    View details for PubMedID 19861642

  • Characterization of X-Linked SNP genotypic variation in globally distributed human populations GENOME BIOLOGY Casto, A. M., Li, J. Z., Absher, D., Myers, R., Ramachandran, S., Feldman, M. W. 2010; 11 (1)

    Abstract

    The transmission pattern of the human X chromosome reduces its population size relative to the autosomes, subjects it to disproportionate influence by female demography, and leaves X-linked mutations exposed to selection in males. As a result, the analysis of X-linked genomic variation can provide insights into the influence of demography and selection on the human genome. Here we characterize the genomic variation represented by 16,297 X-linked SNPs genotyped in the CEPH human genome diversity project samples.We found that X chromosomes tend to be more differentiated between human populations than autosomes, with several notable exceptions. Comparisons between genetically distant populations also showed an excess of X-linked SNPs with large allele frequency differences. Combining information about these SNPs with results from tests designed to detect selective sweeps, we identified two regions that were clear outliers from the rest of the X chromosome for haplotype structure and allele frequency distribution. We were also able to more precisely define the geographical extent of some previously described X-linked selective sweeps.The relationship between male and female demographic histories is likely to be complex as evidence supporting different conclusions can be found in the same dataset. Although demography may have contributed to the excess of SNPs with large allele frequency differences observed on the X chromosome, we believe that selection is at least partially responsible. Finally, our results reveal the geographical complexities of selective sweeps on the X chromosome and argue for the use of diverse populations in studies of selection.

    View details for DOI 10.1186/gb-2010-11-1-r10

    View details for Web of Science ID 000276433600007

    View details for PubMedID 20109212

  • Sociocultural epistasis and cultural exaptation in footbinding, marriage form, and religious practices in early 20th-century Taiwan PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Brown, M. J., Feldman, M. W. 2009; 106 (52): 22139-22144

    Abstract

    Social theorists have long recognized that changes in social order have cultural consequences but have not been able to provide an individual-level mechanism of such effects. Explanations of human behavior have only just begun to explore the different evolutionary dynamics of social and cultural inheritance. Here we provide ethnographic evidence of how cultural evolution, at the level of individuals, can be influenced by social evolution. Sociocultural epistasis--association of cultural ideas with the hierarchical structure of social roles--influences cultural change in unexpected ways. We document the existence of cultural exaptation, where a custom's origin was not due to acceptance of the later associated ideas. A cultural exaptation can develop in the absence of a cultural idea favoring it, or even in the presence of a cultural idea against it. Such associations indicate a potentially larger role for social evolutionary dynamics in explaining individual human behavior than previously anticipated.

    View details for DOI 10.1073/pnas.0907520106

    View details for Web of Science ID 000273178700021

    View details for PubMedID 20080786

  • A theory for the evolution of other-regard integrating proximate and ultimate perspectives PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Akcay, E., Van Cleve, J., Feldman, M. W., Roughgarden, J. 2009; 106 (45): 19061-19066

    Abstract

    Although much previous work describes evolutionary mechanisms that promote or stabilize different social behaviors, we still have little understanding of the factors that drive animal behavior proximately. Here we present a modeling approach to answer this question. Our model rests on motivations to achieve objectives as the proximate determinants of behavior. We develop a two-tiered framework by first modeling the dynamics of a social interaction at the behavioral time scale and then find the evolutionarily stable objectives that result from the outcomes these dynamics produce. We use this framework to ask whether "other-regarding" motivations, which result from a kind of nonselfish objective, can evolve when individuals are engaged in a social interaction that entails a conflict between their material payoffs. We find that, at the evolutionarily stable state, individuals can be other-regarding in that they are motivated to increase their partners' payoff as well as their own. In contrast to previous theories, we find that such motivations can evolve because of their direct effect on fitness and do not require kin selection or a special group structure. We also derive general conditions for the evolutionary stability of other-regarding motivations. Our conditions indicate that other-regarding motivations are more likely to evolve when social interactions and behavioral objectives are both synergistic.

    View details for DOI 10.1073/pnas.0904357106

    View details for Web of Science ID 000271637500035

    View details for PubMedID 19858492

  • Coevolution of adaptive technology, maladaptive culture and population size in a producer-scrounger game PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Lehmann, L., Feldman, M. W. 2009; 276 (1674): 3853-3862

    Abstract

    Technology (i.e. tools, methods of cultivation and domestication, systems of construction and appropriation, machines) has increased the vital rates of humans, and is one of the defining features of the transition from Malthusian ecological stagnation to a potentially perpetual rising population growth. Maladaptations, on the other hand, encompass behaviours, customs and practices that decrease the vital rates of individuals. Technology and maladaptations are part of the total stock of culture carried by the individuals in a population. Here, we develop a quantitative model for the coevolution of cumulative adaptive technology and maladaptive culture in a 'producer-scrounger' game, which can also usefully be interpreted as an 'individual-social' learner interaction. Producers (individual learners) are assumed to invent new adaptations and maladaptations by trial-and-error learning, insight or deduction, and they pay the cost of innovation. Scroungers (social learners) are assumed to copy or imitate (cultural transmission) both the adaptations and maladaptations generated by producers. We show that the coevolutionary dynamics of producers and scroungers in the presence of cultural transmission can have a variety of effects on population carrying capacity. From stable polymorphism, where scroungers bring an advantage to the population (increase in carrying capacity), to periodic cycling, where scroungers decrease carrying capacity, we find that selection-driven cultural innovation and transmission may send a population on the path of indefinite growth or to extinction.

    View details for DOI 10.1098/rspb.2009.0724

    View details for Web of Science ID 000270174800015

    View details for PubMedID 19692409

  • Inferring population histories using cultural data PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Rogers, D. S., Feldman, M. W., Ehrlich, P. R. 2009; 276 (1674): 3835-3843

    Abstract

    The question as to whether cultures evolve in a manner analogous to that of genetic evolution can be addressed by attempting to reconstruct population histories using cultural data. As others have argued, this can only succeed if cultures are isolated enough to maintain and pass on a central core of traditions that can be modified over time. In this study we used a set of cultural data (canoe design traits from Polynesia) to look for the kinds of patterns and relationships normally found in population genetic studies. After developing new techniques to accommodate the peculiarities of cultural data, we were able to infer an ancestral region (Fiji) and a sequence of cultural origins for these Polynesian societies. In addition, we found evidence of cultural exchange, migration and a serial founder effect. Results were stronger when analyses were based on functional traits (presumably subject to natural selection and convergence) rather than symbolic or stylistic traits (probably subject to cultural selection for rapid divergence). These patterns strongly suggest that cultural evolution, while clearly affected by cultural exchange, is also subject to some of the same processes and constraints as genetic evolution.

    View details for DOI 10.1098/rspb.2009.1088

    View details for Web of Science ID 000270174800013

    View details for PubMedID 19675007

  • ON THE EVOLUTION OF HARMING AND RECOGNITION IN FINITE PANMICTIC AND INFINITE STRUCTURED POPULATIONS EVOLUTION Lehmann, L., Feldman, M. W., Rousset, F. 2009; 63 (11): 2896-2913

    Abstract

    Natural selection may favor two very different types of social behaviors that have costs in vital rates (fecundity and/or survival) to the actor: helping behaviors, which increase the vital rates of recipients, and harming behaviors, which reduce the vital rates of recipients. Although social evolutionary theory has mainly dealt with helping behaviors, competition for limited resources creates ecological conditions in which an actor may benefit from expressing behaviors that reduce the vital rates of neighbors. This may occur if the reduction in vital rates decreases the intensity of competition experienced by the actor or that experienced by its offspring. Here, we explore the joint evolution of neutral recognition markers and marker-based costly conditional harming whereby actors express harming, conditional on actor and recipient bearing different conspicuous markers. We do so for two complementary demographic scenarios: finite panmictic and infinite structured populations. We find that marker-based conditional harming can evolve under a large range of recombination rates and group sizes under both finite panmictic and infinite structured populations. A direct comparison with results for the evolution of marker-based conditional helping reveals that, if everything else is equal, marker-based conditional harming is often more likely to evolve than marker-based conditional helping.

    View details for DOI 10.1111/j.1558-5646.2009.00778.x

    View details for Web of Science ID 000271031900011

    View details for PubMedID 19624725

  • Evolution of Stochastic Switching Rates in Asymmetric Fitness Landscapes GENETICS Salathe, M., Van Cleve, J., Feldman, M. W. 2009; 182 (4): 1159-1164

    Abstract

    Uncertain environments pose a tremendous challenge to populations: The selective pressures imposed by the environment can change so rapidly that adaptation by mutation alone would be too slow. One solution to this problem is given by the phenomenon of stochastic phenotype switching, which causes genetically uniform populations to be phenotypically heterogenous. Stochastic phenotype switching has been observed in numerous microbial species and is generally assumed to be an adaptive bet-hedging strategy to anticipate future environmental change. We use an explicit population genetic model to investigate the evolutionary dynamics of phenotypic switching rates. We find that whether or not stochastic switching is an adaptive strategy is highly contingent upon the fitness landscape given by the changing environment. Unless selection is very strong, asymmetric fitness landscapes-where the cost of being maladapted is not identical in all environments-strongly select against stochastic switching. We further observe a threshold phenomenon that causes switching rates to be either relatively high or completely absent, but rarely intermediate. Our finding that marginal changes in selection pressures can cause fundamentally different evolutionary outcomes is important in a wide range of fields concerned with microbial bet hedging.

    View details for DOI 10.1534/genetics.109.103333

    View details for Web of Science ID 000270214000019

    View details for PubMedID 19474199

  • Conceptual Barriers to Progress Within Evolutionary Biology FOUNDATIONS OF SCIENCE Laland, K. N., Odling-Smee, J., Feldman, M. W., Kendal, J. 2009; 14 (3): 195-216
  • The rate at which asexual populations cross fitness valleys THEORETICAL POPULATION BIOLOGY Weissman, D. B., Desai, M. M., Fisher, D. S., Feldman, M. W. 2009; 75 (4): 286-300

    Abstract

    Complex traits often involve interactions between different genetic loci. This can lead to sign epistasis, whereby mutations that are individually deleterious or neutral combine to confer a fitness benefit. In order to acquire the beneficial genotype, an asexual population must cross a fitness valley or plateau by first acquiring the deleterious or neutral intermediates. Here, we present a complete, intuitive theoretical description of the valley-crossing process across the full spectrum of possible parameter regimes. We calculate the rate at which a population crosses a fitness valley or plateau of arbitrary width, as a function of the mutation rates, the population size, and the fitnesses of the intermediates. We find that when intermediates are close to neutral, a large population can cross even wide fitness valleys remarkably quickly, so that valley-crossing dynamics may be common even when mutations that directly increase fitness are also possible. Thus the evolutionary dynamics of large populations can be sensitive to the structure of an extended region of the fitness landscape - the population may not take directly uphill paths in favor of paths across valleys and plateaus that lead eventually to fitter genotypes. In smaller populations, we find that below a threshold size, which depends on the width of the fitness valley and the strength of selection against intermediate genotypes, valley-crossing is much less likely and hence the evolutionary dynamics are less influenced by distant regions of the fitness landscape.

    View details for DOI 10.1016/j.tpb.2009.02.006

    View details for Web of Science ID 000266833500009

    View details for PubMedID 19285994

  • Sam Karlin and multi-locus population genetics THEORETICAL POPULATION BIOLOGY Feldman, M. W. 2009; 75 (4): 233-235

    Abstract

    Between 1967 and 1982, Sam Karlin made fundamental contributions to many areas of deterministic population genetic theory. This remembrance focuses on his work in multi-locus population genetics, primarily on the interaction between genotypic selection and the rate of recombination.

    View details for DOI 10.1016/j.tpb.2009.01.002

    View details for Web of Science ID 000266833500003

    View details for PubMedID 19344629

  • Complementation and Epistasis in Viral Coinfection Dynamics GENETICS Gao, H., Feldman, M. W. 2009; 182 (1): 251-263

    Abstract

    Coinfection in RNA virus populations results in two important phenomena, complementation and recombination. Of the two, complementation has a strong effect on selection against deleterious mutations, as has been confirmed in earlier studies. As complementation delays the purging of less-fit mutations, coinfection may be detrimental to the evolution of a virus population. Here we employ both deterministic modeling and stochastic simulation to explore the mechanisms underlying the interactions between complementation and other evolutionary factors, namely, mutation, selection, and epistasis. We find that strong complementation reduces slightly the overall fitness of a virus population but substantially enhances its diversity and robustness, especially when interacting with selection and epistasis.

    View details for DOI 10.1534/genetics.108.099796

    View details for Web of Science ID 000270213800021

    View details for PubMedID 19270273

  • DYNAMICS OF HYBRID INCOMPATIBILITY IN GENE NETWORKS IN A CONSTANT ENVIRONMENT EVOLUTION Palmer, M. E., Feldman, M. W. 2009; 63 (2): 418-431

    Abstract

    After an ancestral population splits into two allopatric populations, different mutations may fix in each. When pairs of mutations are brought together in a hybrid offspring, epistasis may cause reduced fitness. Such pairs are known as Bateson-Dobzhansky-Muller (BDM) incompatibilities. A well-known model of BDM incompatibility due to Orr suggests that the fitness load on hybrids should initially accelerate, and continue to increase as the number of potentially incompatible substitutions increases (the "snowball effect"). In the gene networks model, which violates a key assumption of Orr's model (independence of fixation probabilities), the snowball effect often does not occur. Instead, we describe three possible dynamics in a constant environment: (1) Stabilizing selection can constrain two allopatric populations to remain near-perfectly compatible. (2) Despite constancy of environment, punctuated evolution may obtain; populations may experience rare adaptations asynchronously, permitting incompatibility. (3) Despite stabilizing selection, developmental system drift may permit genetic change, allowing two populations to drift in and out of compatibility. We reinterpret Orr's model in terms of genetic distance. We extend Orr's model to the finite loci case, which can limit incompatibility. Finally, we suggest that neutral evolution of gene regulation in nature, to the point of speciation, is a distinct possibility.

    View details for DOI 10.1111/j.1558-5646.2008.00577.x

    View details for Web of Science ID 000263254000010

    View details for PubMedID 19215292

  • Topological Signatures of Species Interactions in Metabolic Networks JOURNAL OF COMPUTATIONAL BIOLOGY Borenstein, E., Feldman, M. W. 2009; 16 (2): 191-200

    Abstract

    The topology of metabolic networks can provide insight not only into the metabolic processes that occur within each species, but also into interactions between different species. Here, we introduce a novel pair-wise, topology-based measure of biosynthetic support, reflecting the extent to which the nutritional requirements of one species could be satisfied by the biosynthetic capacity of another. To evaluate the biosynthetic support for a given pair of species, we use a graph-based algorithm to identify the set of exogenously acquired compounds in the metabolic network of the first species, and calculate the fraction of this set that occurs in the metabolic network of the second species. Reconstructing the metabolic network of 569 bacterial species and several eukaryotes, and calculating the biosynthetic support score for all bacterial-eukaryotic pairs, we show that this measure indeed reflects host-parasite interactions and facilitates a successful prediction of such interactions on a large-scale. Integrating this method with phylogenetic analysis and calculating the biosynthetic support of ancestral species in the Firmicutes division (as well as other bacterial divisions) further reveals a large-scale evolutionary trend of biosynthetic capacity loss in parasites. The inference of ecological features from genomic-based data presented here lays the foundations for an exciting "reverse ecology" framework for studying the complex web of interactions characterizing various ecosystems.

    View details for DOI 10.1089/cmb.2008.06TT

    View details for Web of Science ID 000263057400006

    View details for PubMedID 19178139

  • A serial founder effect model for human settlement out of Africa PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Deshpande, O., Batzoglou, S., Feldman, M. W., Cavalli-Sforza, L. L. 2009; 276 (1655): 291-300

    Abstract

    The increasing abundance of human genetic data has shown that the geographical patterns of worldwide genetic diversity are best explained by human expansion out of Africa. This expansion is modelled well by prolonged migration from a single origin in Africa with multiple subsequent serial founding events. We discuss a new simulation model for the serial founder effect out of Africa and compare it with results from previous studies. Unlike previous models, we distinguish colonization events from the continued exchange of people between occupied territories as a result of mating. We conduct a search through parameter space to estimate the range of parameter values that best explain key statistics from published data on worldwide variation in microsatellites. The range of parameters we use is chosen to be compatible with an out-of-Africa migration at 50-60Kyr ago and archaeo-ethno-demographic information. In addition to a colonization rate of 0.09-0.18, for an acceptable fit to the published microsatellite data, incorporation into existing models of exchange between neighbouring populations is essential, but at a very low rate. A linear decay of genetic diversity with geographical distance from the origin of expansion could apply to any species, especially if it moved recently into new geographical niches.

    View details for DOI 10.1098/rspb.2008.0750

    View details for Web of Science ID 000262005200013

    View details for PubMedID 18796400

  • Characterizing the Time Dependency of Human Mitochondrial DNA Mutation Rate Estimates MOLECULAR BIOLOGY AND EVOLUTION Henn, B. M., Gignoux, C. R., Feldman, M. W., Mountain, J. L. 2009; 26 (1): 217-230

    Abstract

    Previous research has established a discrepancy of nearly an order of magnitude between pedigree-based and phylogeny-based (human vs. chimpanzee) estimates of the mitochondrial DNA (mtDNA) control region mutation rate. We characterize the time dependency of the human mitochondrial hypervariable region one mutation rate by generating 14 new phylogeny-based mutation rate estimates using within-human comparisons and archaeological dates. Rate estimates based on population events between 15,000 and 50,000 years ago are at least 2-fold lower than pedigree-based estimates. These within-human estimates are also higher than estimates generated from phylogeny-based human-chimpanzee comparisons. Our new estimates establish a rapid decay in evolutionary mutation rate between approximately 2,500 and 50,000 years ago and a slow decay from 50,000 to 6 Ma. We then extend this analysis to the mtDNA-coding region. Our within-human coding region mutation rate estimates display a similar, though less rapid, time-dependent decay. We explore the possibility that multiple hits explain the discrepancy between pedigree-based and phylogeny-based mutation rates. We conclude that whereas nucleotide substitution models incorporating multiple hits do provide a possible explanation for the discrepancy between pedigree-based and human-chimpanzee mutation rate estimates, they do not explain the rapid decline of within-human rate estimates. We propose that demographic processes such as serial bottlenecks prior to the Holocene could explain the difference between rates estimated before and after 15,000 years ago. Our findings suggest that human mtDNA estimates of dates of population and phylogenetic events should be adjusted in light of this time dependency of the mutation rate estimates.

    View details for DOI 10.1093/molbev/msn244

    View details for Web of Science ID 000261681900021

    View details for PubMedID 18984905

  • War and the evolution of belligerence and bravery PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Lehmann, L., Feldman, M. W. 2008; 275 (1653): 2877-2885

    Abstract

    Tribal war occurs when a coalition of individuals use force to seize reproduction-enhancing resources, and it may have affected human evolution. Here, we develop a population-genetic model for the coevolution of costly male belligerence and bravery when war occurs between groups of individuals in a spatially subdivided population. Belligerence is assumed to increase an actor's group probability of trying to conquer another group. An actor's bravery is assumed to increase his group's ability to conquer an attacked group. We show that the selective pressure on these two traits can be substantial even in groups of large size, and that they may be driven by two independent reproduction-enhancing resources: additional mates for males and additional territory (or material resources) for females. This has consequences for our understanding of the evolution of intertribal interactions, as hunter-gatherer societies are well known to have frequently raided neighbouring groups from whom they appropriated territory, goods and women.

    View details for DOI 10.1098/rspb.2008.0842

    View details for Web of Science ID 000260611200012

    View details for PubMedID 18755675

  • Economics, cultural transmission, and the dynamics of the sex ratio at birth in China PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Lipatov, M., Li, S., Feldman, M. W. 2008; 105 (49): 19171-19176

    Abstract

    In rural China, the ratio of newborn boys to newborn girls [sex ratio at birth (SRB)] has been rising for several decades, to values significantly above its biological norm. This trend has a number of alarming societal consequences, and has attracted the attention of scholars and politicians. The root of the problem lies in a 2,500-year-old culture of son preference. This culture is intricately linked with the economic reality of each couple's life, so that there are financial and psychological repercussions to parents who have no sons. To bring greater clarity and understanding to this issue, we present a quantitative framework that describes the interaction between economics and cultural transmission. We start with an explicit mechanism by which economic incentives can change cultural beliefs of a given individual, and go on to include a mechanism of cultural inheritance from generation to generation. We then show how economic conditions can affect the dynamics of cultural change in an entire society, and may lead to a decrease in the country's sex ratio at birth.

    View details for DOI 10.1073/pnas.0806747105

    View details for Web of Science ID 000261706600029

    View details for PubMedID 19047641

  • High Functional Diversity in Mycobacterium tuberculosis Driven by Genetic Drift and Human Demography PLOS BIOLOGY Hershberg, R., Lipatov, M., Small, P. M., Sheffer, H., Niemann, S., Homolka, S., Roach, J. C., Kremer, K., Petrov, D. A., Feldman, M. W., Gagneux, S. 2008; 6 (12): 2658-2671

    Abstract

    Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. tuberculosis complex (MTBC). However, all human-adapted strains of MTBC have traditionally been considered to be essentially identical. We surveyed sequence diversity within a global collection of strains belonging to MTBC using seven megabase pairs of DNA sequence data. We show that the members of MTBC affecting humans are more genetically diverse than generally assumed, and that this diversity can be linked to human demographic and migratory events. We further demonstrate that these organisms are under extremely reduced purifying selection and that, as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences. Our findings suggest that the current increases in human population, urbanization, and global travel, combined with the population genetic characteristics of M. tuberculosis described here, could contribute to the emergence and spread of drug-resistant tuberculosis.

    View details for DOI 10.1371/journal.pbio.0060311

    View details for Web of Science ID 000261913700009

    View details for PubMedID 19090620

  • Social and individual learning of helping in humans and other species TRENDS IN ECOLOGY & EVOLUTION Lehmann, L., Foster, K. R., Borenstein, E., Feldman, M. W. 2008; 23 (12): 664-671

    Abstract

    Helping behaviors can be innate, learned by copying others (cultural transmission) or individually learned de novo. These three possibilities are often entangled in debates on the evolution of helping in humans. Here we discuss their similarities and differences, and argue that evolutionary biologists underestimate the role of individual learning in the expression of helping behaviors in humans.

    View details for DOI 10.1016/j.tree.2008.07.012

    View details for Web of Science ID 000261532300004

    View details for PubMedID 18951656

  • How can economic schemes curtail the increasing sex ratio at birth in China? DEMOGRAPHIC RESEARCH Bhattacharjya, D., Sudarshan, A., Tuljapurkar, S., Shachter, R., Feldman, M. 2008; 19: 1831-1850

    Abstract

    Fertility decline, driven by the one-child policy, and son preference have contributed to an alarming difference in the number of live male and female births in China. We present a quantitative model where people choose to sex-select because they perceive that married sons are more valuable than married daughters. Due to the predominant patrilocal kinship system in China, daughters-in-law provide valuable emotional and financial support, enhancing the perceived present value of married sons. We argue that inter-generational transfer data will help ascertain the extent to which economic schemes (such as pension plans for families with no sons) can curtail the increasing sex ratio at birth.

    View details for Web of Science ID 000259977900001

    View details for PubMedID 21113272

  • Large-scale reconstruction and phylogenetic analysis of metabolic environments PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Borenstein, E., Kupiec, M., Feldman, M. W., Ruppin, E. 2008; 105 (38): 14482-14487

    Abstract

    The topology of metabolic networks may provide important insights not only into the metabolic capacity of species, but also into the habitats in which they evolved. Here we introduce the concept of a metabolic network's "seed set"--the set of compounds that, based on the network topology, are exogenously acquired--and provide a methodological framework to computationally infer the seed set of a given network. Such seed sets form ecological "interfaces" between metabolic networks and their surroundings, approximating the effective biochemical environment of each species. Analyzing the metabolic networks of 478 species and identifying the seed set of each species, we present a comprehensive large-scale reconstruction of such predicted metabolic environments. The seed sets' composition significantly correlates with several basic properties characterizing the species' environments and agrees with biological observations concerning major adaptations. Species whose environments are highly predictable (e.g., obligate parasites) tend to have smaller seed sets than species living in variable environments. Phylogenetic analysis of the seed sets reveals the complex dynamics governing gain and loss of seeds across the phylogenetic tree and the process of transition between seed and non-seed compounds. Our findings suggest that the seed state is transient and that seeds tend either to be dropped completely from the network or to become non-seed compounds relatively fast. The seed sets also permit a successful reconstruction of a phylogenetic tree of life. The "reverse ecology" approach presented lays the foundations for studying the evolutionary interplay between organisms and their habitats on a large scale.

    View details for DOI 10.1073/pnas.0806162105

    View details for Web of Science ID 000259592400047

    View details for PubMedID 18787117

  • Stable long-period cycling and complex dynamics in a single-locus fertility model with genomic imprinting JOURNAL OF MATHEMATICAL BIOLOGY Van Cleve, J., Feldman, M. W. 2008; 57 (2): 243-264

    Abstract

    Although long-period population size cycles and chaotic fluctuations in abundance are common in ecological models, such dynamics are uncommon in simple population-genetic models where convergence to a fixed equilibrium is most typical. When genotype-frequency cycling does occur, it is most often due to frequency-dependent selection that results from individual or species interactions. In this paper, we demonstrate that fertility selection and genomic imprinting are sufficient to generate a Hopf bifurcation and complex genotype-frequency cycling in a single-locus population-genetic model. Previous studies have shown that on its own, fertility selection can yield stable two-cycles but not long-period cycling characteristic of a Hopf bifurcation. Genomic imprinting, a molecular mechanism by which the expression of an allele depends on the sex of the donating parent, allows fitness matrices to be nonsymmetric, and this additional flexibility is crucial to the complex dynamics we observe in this fertility selection model. Additionally, we find under certain conditions that stable oscillations and a stable equilibrium point can coexist. These dynamics are characteristic of a Chenciner (generalized Hopf) bifurcation. We believe this model to be the simplest population-genetic model with such dynamics.

    View details for DOI 10.1007/s00285-008-0156-4

    View details for Web of Science ID 000255863900005

    View details for PubMedID 18253736

  • Cultural transmission can inhibit the evolution of altruistic helping AMERICAN NATURALIST Lehmann, L., Feldman, M. W., Foster, K. R. 2008; 172 (1): 12-24

    Abstract

    The study of culturally inherited traits has led to the suggestion that the evolution of helping behaviors is more likely with cultural transmission than without. Here we evaluate this idea through a comparative analysis of selection on helping under both genetic and cultural inheritance. We develop two simple models for the evolution of helping through cultural group selection: one in which selection on the trait depends solely on Darwinian fitness effects and one in which selection is driven by nonreproductive factors, specifically imitation of strategies achieving higher payoffs. We show that when cultural variants affect Darwinian fitness, the selection pressure on helping can be markedly increased relative to that under genetic transmission. By contrast, when variants are driven by nonreproductive factors, the selection pressure on helping may be reduced relative to that under genetic inheritance. This occurs because, unlike biological offspring, the spread of cultural variants from one group to another through imitation does not reduce the number of these variants in the source group. As a consequence, there is increased within-group competition associated with traits increasing group productivity, which reduces the benefits of helping. In these cases, selection for harming behavior (decreasing the payoff to neighbors) may occur rather than selection for helping.

    View details for DOI 10.1086/587851

    View details for Web of Science ID 000256752600005

    View details for PubMedID 18500938

  • The co-evolution of culturally inherited altruistic helping and cultural transmission under random group formation THEORETICAL POPULATION BIOLOGY Lehmann, L., Feldman, M. W. 2008; 73 (4): 506-516

    Abstract

    Limited migration results in kin selective pressure on helping behaviors under a wide range of ecological, demographic and life-history situations. However, such genetically determined altruistic helping can evolve only when migration is not too strong and group size is not too large. Cultural inheritance of helping behaviors may allow altruistic helping to evolve in groups of larger size because cultural transmission has the potential to markedly decrease the variance within groups and augment the variance between groups. Here, we study the co-evolution of culturally inherited altruistic helping behaviors and two alternative cultural transmission rules for such behaviors. We find that conformist transmission, where individuals within groups tend to copy prevalent cultural variants (e.g., beliefs or values), has a strong adverse effect on the evolution of culturally inherited helping traits. This finding is at variance with the commonly held view that conformist transmission is a crucial factor favoring the evolution of altruistic helping in humans. By contrast, we find that under one-to-many transmission, where individuals within groups tend to copy a "leader" (or teacher), altruistic helping can evolve in groups of any size, although the cultural transmission rule itself hitchhikes rather weakly with a selected helping trait. Our results suggest that culturally determined helping behaviors are more likely to be driven by "leaders" than by popularity, but the emergence and stability of the cultural transmission rules themselves should be driven by some extrinsic factors.

    View details for DOI 10.1016/j.tpb.2008.02.004

    View details for Web of Science ID 000256996000006

    View details for PubMedID 18420241

  • Evolution of learning in fluctuating environments: When selection favors both social and exploratory individual learning EVOLUTION Borenstein, E., Feldman, M. W., Aoki, K. 2008; 62 (3): 586-602

    Abstract

    Cumulative cultural change requires organisms that are capable of both exploratory individual learning and faithful social learning. In our model, an organism's phenotype is initially determined innately (by its genotypic value) or by social learning (copying a phenotype from the parental generation), and then may or may not be modified by individual learning (exploration around the initial phenotype). The environment alternates periodically between two states, each defined as a certain range of phenotypes that can survive. These states may overlap, in which case the same phenotype can survive in both states, or they may not. We find that a joint social and exploratory individual learning strategy-the strategy that supports cumulative culture-is likely to spread when the environmental states do not overlap. In particular, when the environmental states are contiguous and mutation is allowed among the genotypic values, this strategy will spread in either moderately or highly stable environments, depending on the exact nature of the individual learning applied. On the other hand, natural selection often favors a social learning strategy without exploration when the environmental states overlap. We find only partial support for the "consensus" view, which holds that individual learning, social learning, and innate determination of behavior will evolve at short, intermediate, and long environmental periodicities, respectively.

    View details for DOI 10.1111/j.1558-5646.2007.00313.x

    View details for Web of Science ID 000253758600008

    View details for PubMedID 18182074

  • Worldwide human relationships inferred from genome-wide patterns of variation SCIENCE Li, J. Z., Absher, D. M., Tang, H., Southwick, A. M., Casto, A. M., Ramachandran, S., Cann, H. M., Barsh, G. S., Feldman, M., Cavalli-Sforza, L. L., Myers, R. M. 2008; 319 (5866): 1100-1104

    Abstract

    Human genetic diversity is shaped by both demographic and biological factors and has fundamental implications for understanding the genetic basis of diseases. We studied 938 unrelated individuals from 51 populations of the Human Genome Diversity Panel at 650,000 common single-nucleotide polymorphism loci. Individual ancestry and population substructure were detectable with very high resolution. The relationship between haplotype heterozygosity and geography was consistent with the hypothesis of a serial founder effect with a single origin in sub-Saharan Africa. In addition, we observed a pattern of ancestral allele frequency distributions that reflects variation in population dynamics among geographic regions. This data set allows the most comprehensive characterization to date of human genetic variation.

    View details for DOI 10.1126/science.1153717

    View details for Web of Science ID 000253311700046

    View details for PubMedID 18292342

  • The ethics of characterizing difference: guiding principles on using racial categories in human genetics GENOME BIOLOGY Lee, S. S., Mountain, J., Koenig, B., Altman, R., Brown, M., Camarillo, A., Cavalli-Sforza, L., Cho, M., Eberhardt, J., Feldman, M., Ford, R., Greely, H., King, R., Markus, H., Satz, D., Snipp, M., Steele, C., Underhill, P. 2008; 9 (7)

    Abstract

    We are a multidisciplinary group of Stanford faculty who propose ten principles to guide the use of racial and ethnic categories when characterizing group differences in research into human genetic variation.

    View details for DOI 10.1186/gb-2008-9-7-404

    View details for Web of Science ID 000258773600005

    View details for PubMedID 18638359

  • An exact nonparametric method for inferring mosaic structure in sequence triplets GENETICS Boni, M. F., Posada, D., Feldman, M. W. 2007; 176 (2): 1035-1047

    Abstract

    Statistical tests for detecting mosaic structure or recombination among nucleotide sequences usually rely on identifying a pattern or a signal that would be unlikely to appear under clonal reproduction. Dozens of such tests have been described, but many are hampered by long running times, confounding of selection and recombination, and/or inability to isolate the mosaic-producing event. We introduce a test that is exact, nonparametric, rapidly computable, free of the infinite-sites assumption, able to distinguish between recombination and variation in mutation/fixation rates, and able to identify the breakpoints and sequences involved in the mosaic-producing event. Our test considers three sequences at a time: two parent sequences that may have recombined, with one or two breakpoints, to form the third sequence (the child sequence). Excess similarity of the child sequence to a candidate recombinant of the parents is a sign of recombination; we take the maximum value of this excess similarity as our test statistic Delta(m,n,b). We present a method for rapidly calculating the distribution of Delta(m,n,b) and demonstrate that it has comparable power to and a much improved running time over previous methods, especially in detecting recombination in large data sets.

    View details for DOI 10.1534/genetics.106.068874

    View details for Web of Science ID 000247870700027

    View details for PubMedID 17409078

  • Sex-specific viability, sex linkage and dominance in genomic imprinting GENETICS Van Cleve, J., Feldman, M. W. 2007; 176 (2): 1101-1118

    Abstract

    Genomic imprinting is a phenomenon by which the expression of an allele at a locus depends on the parent of origin. Two different two-locus evolutionary models are presented in which a second locus modifies the imprinting status of the primary locus, which is under differential selection in males and females. In the first model, a modifier allele that imprints the primary locus invades the population when the average dominance coefficient among females and males is >12 and selection is weak. The condition for invasion is always heavily contingent upon the extent of dominance. Imprinting is more likely in the sex experiencing weaker selection only under some parameter regimes, whereas imprinting by either sex is equally likely under other regimes. The second model shows that a modifier allele that induces imprinting will increase when imprinting has a direct selective advantage. The results are not qualitatively dependent on whether the modifier locus is autosomal or X linked.

    View details for DOI 10.1534/genetics.107.071555

    View details for Web of Science ID 000247870700031

    View details for PubMedID 17435253

  • Genetic diversity and population structure inferred from the partially duplicated genome of domesticated carp, Cyprinus carpio L. GENETICS SELECTION EVOLUTION David, L., Rosenberg, N. A., Lavi, U., Feldman, M. W., Hillel, J. 2007; 39 (3): 319-340

    Abstract

    Genetic relationships among eight populations of domesticated carp (Cyprinus carpio L.), a species with a partially duplicated genome, were studied using 12 microsatellites and 505 AFLP bands. The populations included three aquacultured carp strains and five ornamental carp (koi) variants. Grass carp (Ctenopharyngodon idella) was used as an outgroup. AFLP-based gene diversity varied from 5% (grass carp) to 32% (koi) and reflected the reasonably well understood histories and breeding practices of the populations. A large fraction of the molecular variance was due to differences between aquacultured and ornamental carps. Further analyses based on microsatellite data, including cluster analysis and neighbor-joining trees, supported the genetic distinctiveness of aquacultured and ornamental carps, despite the recent divergence of the two groups. In contrast to what was observed for AFLP-based diversity, the frequency of heterozygotes based on microsatellites was comparable among all populations. This discrepancy can potentially be explained by duplication of some loci in Cyprinus carpio L., and a model that shows how duplication can increase heterozygosity estimates for microsatellites but not for AFLP loci is discussed. Our analyses in carp can help in understanding the consequences of genotyping duplicated loci and in interpreting discrepancies between dominant and co-dominant markers in species with recent genome duplication.

    View details for DOI 10.1051/gse:2007006

    View details for Web of Science ID 000245686900006

    View details for PubMedID 17433244

  • On the evolution of epistasis II: A generalized Wright-Kimura framework THEORETICAL POPULATION BIOLOGY Liberman, U., Puniyani, A., Feldman, M. W. 2007; 71 (2): 230-238

    Abstract

    The evolution of fitness interactions between genes at two major loci is studied where the alleles at a third locus modify the epistatic interaction between the two major loci. The epistasis is defined by a parameter epsilon and a matrix structure that specifies the nature of the interactions. When epsilon=0 the two major loci have additive fitnesses, and when these are symmetric the interaction matrices studied here produce symmetric viabilities of the Wright [1952. The genetics of quantitative variability. In: Reeve, E.C.R., Waddington, C.H. (Eds.), Quantitative Inheritance. Her Majesty's Stationary Office, London]-Kimura [1956. A model of a genetic system which leads to closer linkage by natural selection. Evolution 10, 278-281] form. Two such interaction matrices are studied, for one of which epistasis as measured by |epsilon| always increases, and for the other it increases when the linkage between the major loci is tight enough and there is initial linkage disequilibrium. Increase of epistasis does not necessarily coincide with increase in equilibrium mean fitness.

    View details for DOI 10.1016/j.tpb.2006.10.002

    View details for Web of Science ID 000244907800009

    View details for PubMedID 17141817

  • Detection of agriculturally important QTLs in chickens and analysis of the factors affecting genotyping strategy CYTOGENETIC AND GENOME RESEARCH Atzmon, G., Blum, S., Feldman, M., Lavi, U., Hillel, J. 2007; 117 (1-4): 327-337

    Abstract

    Three single cross populations were generated in order to analyze factors affecting the ability to detect true linkage with minimum false positive or false negative associations, and to detect associations between markers and quantitative traits. The three populations are: (1) a broiler x broiler cross of a single sire and 34 dams, resulting in 266 progeny; (2) a broiler x broiler cross of a single sire and 41 dams resulting in 360 progeny; and (3) a broiler x layer cross of a single sire with 56 dams resulting in 1180 progeny. Based on these three resource populations we show that: a) gradient selective genotyping was more effective than the random selective genotyping; b) selective genotyping was significant at a selected proportion less than 62% of the cumulative truncation point; c) as few as 10% of selected individuals (5% of each of the two tails) were sufficient to show significant association between markers and phenotypes; d) a gradient slices approach was more powerful than using replicates of the extreme groups; and e) in resource populations resulting from crosses between lines of different backgrounds, most of the microsatellite markers used are polymorphic. We also used simulation to test factors affecting power to detect true associations between markers and traits that are hard to detect in experimental resource populations. Using defined populations in the simulation, we concluded that the following guidelines provide reliable detection of linked QTLs: 1) the resource population size should be larger than 100; 2) a QTL effect larger than 0.4 SD is detectable with a reasonable number of markers (>100) and resource population size (>200 subjects); 3) the DNA pool from each tail of the trait distribution should contain at least 10% of the resource family; 4) each of the two DNA pools should include more than 35 individuals. Some of these guidelines that were deduced from the simulation analysis have been confirmed in the experimental part of this study.

    View details for DOI 10.1159/000103195

    View details for Web of Science ID 000249980800038

    View details for PubMedID 17675875

  • Difference between evolutionarily effective and germ line mutation rate due to stochastically varying haplogroup size MOLECULAR BIOLOGY AND EVOLUTION Zhivotovsky, L. A., Underhill, P. A., Feldman, M. W. 2006; 23 (12): 2268-2270

    Abstract

    Within a Y-chromosome haplogroup defined by unique event mutations, variation in microsatellites can accumulate due to their rapid mutation. Estimates based on pedigrees for the Y-chromosome microsatellite mutation rate are 3 or more times greater than the same estimates from evolutionary considerations. We show by simulation that the haplogroups that survive the stochastic processes of drift and extinction accumulate microsatellite variation at a lower rate than predicted from corresponding pedigree estimates; in particular, under constant total population size, the accumulated variance is on average 3-4 times smaller.

    View details for DOI 10.1093/molbev/msl1105

    View details for Web of Science ID 000241955400003

    View details for PubMedID 16956974

  • Cultural coevolution of norm adoption and enforcement when punishers are rewarded or non-punishers are punished THEORETICAL POPULATION BIOLOGY Kendal, J., Feldman, M. W., Aoki, K. 2006; 70 (1): 10-25

    Abstract

    A number of studies have shown that social norms can be maintained at a high frequency when norm-violators are punished. However, there remains the problem of how norm-adopters and punishers coevolve within a single group. We develop a recursive system to examine the coevolution of norm-adopters and punishers where the viability of punishers is enhanced by one of two "metanorms": (1) Norm-observers reward punishers for punishing norm-violators (Reward Model); (2) Punishers punish non-punishers (Punishment Model). Both models generate a bistable system and each is characterized in phenotype frequency space by a distinct region of attraction to the equilibrium consisting of only norm-adopting punishers. Using a Monte Carlo simulation, we find that cultural drift may allow norm-adopters and punishers to coevolve from invasion into this region of attraction, resulting in their fixation. This coevolution typically occurs across a wider range of conditions under the reward- than the punishment-based metanorm. We also show that, under appropriate conditions, a large negative statistical association between the two traits may evolve only under the Reward Model. Furthermore, for each metanorm, a population of norm-adopters who always observe the norm can be locally stable over a continuum of punishment frequencies.

    View details for DOI 10.1016/j.tpb.2006.01.003

    View details for Web of Science ID 000238628900002

    View details for PubMedID 16516942

  • Cultural Niche Construction in a metapopulation THEORETICAL POPULATION BIOLOGY Borenstein, E., Kendal, J., Feldman, M. 2006; 70 (1): 92-104

    Abstract

    Cultural niche construction is the process by which certain evolving cultural traits form a cultural niche that affects the evolution of other genetic and cultural traits [Laland, K., et al., 2001. Cultural niche construction and human evolution. J. Evol. Biol. 14, 22-33; Ihara, Y., Feldman, M., 2004. Cultural niche construction and the evolution of small family size. Theor. Popul. Biol. 65, 105-111]. In this study we focus on cultural niche construction in a metapopulation (a population of populations), where the frequency of one cultural trait (e.g. the level of education) determines the transmission rate of a second trait (e.g. the adoption of fertility reduction preferences) within and between populations. We formulate the Metapopulation Cultural Niche Construction (MPCNC) model by defining the cultural niche induced by the first trait as the construction of a social interaction network on which the second trait may percolate. Analysis of the model reveals dynamics that are markedly different from those observed in a single population, allowing, for example, different (or even opposing) dynamics in each population. In particular, this model can account for the puzzling phenomenon reported in previous studies [Bongaarts, J., Watkins, S., 1996. Social interactions and contemporary fertility transitions. Popul. Dev. Rev. 22 (4), 639-682] that the onset of the demographic transition in different countries occurred at ever lower levels of development.

    View details for DOI 10.1016/j.tpb.2005.10.003

    View details for Web of Science ID 000238628900009

    View details for PubMedID 16426653

  • Epidemic dynamics and antigenic evolution in a single season of influenza A PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Boni, M. F., Gog, J. R., Andreasen, V., Feldman, M. W. 2006; 273 (1592): 1307-1316

    Abstract

    We use a mathematical model to study the evolution of influenza A during the epidemic dynamics of a single season. Classifying strains by their distance from the epidemic-originating strain, we show that neutral mutation yields a constant rate of antigenic evolution, even in the presence of epidemic dynamics. We introduce host immunity and viral immune escape to construct a non-neutral model. Our population dynamics can then be framed naturally in the context of population genetics, and we show that departure from neutrality is governed by the covariance between a strain's fitness and its distance from the original epidemic strain. We quantify the amount of antigenic evolution that takes place in excess of what is expected under neutrality and find that this excess amount is largest under strong host immunity and long epidemics.

    View details for DOI 10.1098/rspb.2006.3466

    View details for Web of Science ID 000237780100001

    View details for PubMedID 16777717

  • Why is stress so deadly? An evolutionary perspective PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Hadany, L., Beker, T., Eshel, I., Feldman, M. W. 2006; 273 (1588): 881-885

    Abstract

    The reaction of the body to prolonged stress has many harmful effects. Classical theory assumes that stress responses have evolved due to their short-term selective advantages ('flight or fight'), and despite their adverse long-term effects. In contrast, we demonstrate that the adverse effects of stress responses may have a selective advantage. Using an analytical model we show that a gene that causes the early death of a relatively unfit individual can increase in frequency in a structured population even if it has no positive effect on that individual. This result offers a new perspective on the relations between stress factors, stress responses and stress-related diseases.

    View details for DOI 10.1098/rspb.2005.3384

    View details for Web of Science ID 000236279800016

    View details for PubMedID 16618683

  • A semi-symmetric two-locus model THEORETICAL POPULATION BIOLOGY Puniyani, A., Feldman, M. W. 2006; 69 (2): 211-215

    Abstract

    The two-locus symmetric viability model characterized by its invariance with respect to the exchange of alleles at each locus, is a well-studied model of classical two-locus theory. The symmetric model introduced by Lewontin and Kojima is among the few multi-locus models with epistatic interactions between loci for which a polymorphism with linkage equilibrium can be stable and this happens when recombination is sufficiently large. We show that an analogous property holds true for a different model, in which symmetry need exist at only one locus. The properties of this new semi-symmetric model are compared with those of the classical symmetric model. For tight linkage, two classes of polymorphisms are possible, depending on the magnitude of additive epistasis. The recombination rate above which linkage equilibrium becomes stable is derived analytically. As in the symmetric model, intervals of recombination in which no polymorphism is stable are possible, and stable polymorphisms can coexist with stable fixations.

    View details for DOI 10.1016/j.tpb.2005.07.004

    View details for Web of Science ID 000235325500010

    View details for PubMedID 16256158

  • The role of selection in the evolution of human mitochondrial genomes GENETICS Kivisild, T., Shen, P. D., Wall, D. P., Do, B., Sung, R., Davis, K., Passarino, G., Underhill, P. A., Scharfe, C., Torroni, A., Scozzari, R., Modiano, D., Coppa, A., de Knijff, P., Feldman, M., Cavalli-Sforza, L. L., Oefner, P. J. 2006; 172 (1): 373-387

    Abstract

    High mutation rate in mammalian mitochondrial DNA generates a highly divergent pool of alleles even within species that have dispersed and expanded in size recently. Phylogenetic analysis of 277 human mitochondrial genomes revealed a significant (P < 0.01) excess of rRNA and nonsynonymous base substitutions among hotspots of recurrent mutation. Most hotspots involved transitions from guanine to adenine that, with thymine-to-cytosine transitions, illustrate the asymmetric bias in codon usage at synonymous sites on the heavy-strand DNA. The mitochondrion-encoded tRNAThr varied significantly more than any other tRNA gene. Threonine and valine codons were involved in 259 of the 414 amino acid replacements observed. The ratio of nonsynonymous changes from and to threonine and valine differed significantly (P = 0.003) between populations with neutral (22/58) and populations with significantly negative Tajima's D values (70/76), independent of their geographic location. In contrast to a recent suggestion that the excess of nonsilent mutations is characteristic of Arctic populations, implying their role in cold adaptation, we demonstrate that the surplus of nonsynonymous mutations is a general feature of the young branches of the phylogenetic tree, affecting also those that are found only in Africa. We introduce a new calibration method of the mutation rate of synonymous transitions to estimate the coalescent times of mtDNA haplogroups.

    View details for DOI 10.1534/genetics.105.043901

    View details for Web of Science ID 000235197700033

    View details for PubMedID 16172508

  • Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Ramachandran, S., Deshpande, O., Roseman, C. C., Rosenberg, N. A., Feldman, M. W., Cavalli-Sforza, L. L. 2005; 102 (44): 15942-15947

    Abstract

    Equilibrium models of isolation by distance predict an increase in genetic differentiation with geographic distance. Here we find a linear relationship between genetic and geographic distance in a worldwide sample of human populations, with major deviations from the fitted line explicable by admixture or extreme isolation. A close relationship is shown to exist between the correlation of geographic distance and genetic differentiation (as measured by F(ST)) and the geographic pattern of heterozygosity across populations. Considering a worldwide set of geographic locations as possible sources of the human expansion, we find that heterozygosities in the globally distributed populations of the data set are best explained by an expansion originating in Africa and that no geographic origin outside of Africa accounts as well for the observed patterns of genetic diversity. Although the relationship between F(ST) and geographic distance has been interpreted in the past as the result of an equilibrium model of drift and dispersal, simulation shows that the geographic pattern of heterozygosities in this data set is consistent with a model of a serial founder effect starting at a single origin. Given this serial-founder scenario, the relationship between genetic and geographic distance allows us to derive bounds for the effects of drift and natural selection on human genetic variation.

    View details for Web of Science ID 000233090900042

    View details for PubMedID 16243969

  • Functional genomic analysis of the rates of protein evolution PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Wall, D. P., Hirsh, A. E., Fraser, H. B., Kumm, J., Giaever, G., Eisen, M. B., Feldman, M. W. 2005; 102 (15): 5483-5488

    Abstract

    The evolutionary rates of proteins vary over several orders of magnitude. Recent work suggests that analysis of large data sets of evolutionary rates in conjunction with the results from high-throughput functional genomic experiments can identify the factors that cause proteins to evolve at such dramatically different rates. To this end, we estimated the evolutionary rates of >3,000 proteins in four species of the yeast genus Saccharomyces and investigated their relationship with levels of expression and protein dispensability. Each protein's dispensability was estimated by the growth rate of mutants deficient for the protein. Our analyses of these improved evolutionary and functional genomic data sets yield three main results. First, dispensability and expression have independent, significant effects on the rate of protein evolution. Second, measurements of expression levels in the laboratory can be used to filter data sets of dispensability estimates, removing variates that are unlikely to reflect real biological effects. Third, structural equation models show that although we may reasonably infer that dispensability and expression have significant effects on protein evolutionary rate, we cannot yet accurately estimate the relative strengths of these effects.

    View details for DOI 10.1073/pnas.0501761102

    View details for Web of Science ID 000228376600036

    View details for PubMedID 15800036

  • Evolution of antibiotic resistance by human and bacterial niche construction EVOLUTION Boni, M. F., Feldman, M. W. 2005; 59 (3): 477-491

    Abstract

    Antibiotic treatment by humans generates strong viability selection for antibiotic-resistant bacterial strains. The frequency of host antibiotic use often determines the strength of this selection, and changing patterns of antibiotic use can generate many types of behaviors in the population dynamics of resistant and sensitive bacterial populations. In this paper, we present a simple model of hosts dimorphic for their tendency to use/avoid antibiotics and bacterial pathogens dimorphic in their resistance/sensitivity to antibiotic treatment. When a constant fraction of hosts uses antibiotics, the two bacterial strain populations can coexist unless host use-frequency is above a critical value; this critical value is derived as the ratio of the fitness cost of resistance to the fitness cost of undergoing treatment. When strain frequencies can affect host behavior, the dynamics may be analyzed in the light of niche construction. We consider three models underlying changing host behavior: conformism, the avoidance of long infections, and adherence to the advice of public health officials. In the latter two, we find that the pathogen can have quite a strong effect on host behavior. In particular, if antibiotic use is discouraged when resistance levels are high, we observe a classic niche-construction phenomenon of maintaining strain polymorphism even in parameter regions where it would not be expected.

    View details for Web of Science ID 000227943400001

    View details for PubMedID 15856691

  • Evolutionary traction: the cost of adaptation and the evolution of sex JOURNAL OF EVOLUTIONARY BIOLOGY Hadany, L., Feldman, M. W. 2005; 18 (2): 309-314

    Abstract

    The advantage of sexual reproduction remains a puzzle for evolutionary biologists. Everything else being equal, asexual populations are expected to have twice the number of offspring produced by similar sexual populations. Yet, asexual species are uncommon among higher eukaryotes. In models assuming small populations, high mutation rates, or frequent environmental changes, sexual reproduction seems to have at least a two-fold advantage over asexuality. But the advantage of sex for large populations, low mutation rates, and rare or mild environmental changes remains a conundrum. Here we show that without recombination, rare advantageous mutations can result in increased accumulation of deleterious mutations ('evolutionary traction'), which explains the long-term advantage of sex under a wide parameter range.

    View details for DOI 10.1111/j.1420-9101.2004.00858.x

    View details for Web of Science ID 000227017400007

    View details for PubMedID 15715837

  • On the meaning of non-epistatic selection THEORETICAL POPULATION BIOLOGY Puniyani, A., Liberman, U., Feldman, M. W. 2004; 66 (4): 317-321

    Abstract

    In population genetics, the additive and multiplicative viability models are often used for the quantitative description of models in which the genetic contributions of several different loci are independent; that is, there is no epistasis. Non-epistasis may also be quantitatively defined in terms of measures of interaction used widely in statistics. Setting these measures of epistasis to zero yields alternative definitions of non-epistasis. We show here that these two definitions of non-epistasis are equivalent; that is, in the most general case of a multilocus, multiallele system, the additive and multiplicative viability models are unique solutions of the additive and multiplicative conditions, respectively, for non-epistasis.

    View details for DOI 10.1016/j.tpb.2004.05.001

    View details for Web of Science ID 000225649600004

    View details for PubMedID 15560910

  • Demographic estimates from Y chromosome microsatellite polymorphisms: analysis of a worldwide sample. Human genomics Macpherson, J. M., Ramachandran, S., Diamond, L., Feldman, M. W. 2004; 1 (5): 345-354

    Abstract

    Polymorphisms in microsatellites on the human Y chromosome have been used to estimate important demographic parameters of human history. We compare two coalescent-based statistical methods that give estimates for a number of demographic parameters using the seven Y chromosome polymorphisms in the HGDP-CEPH Cell Line Panel, a collection of samples from 52 worldwide populations. The estimates for the time to the most recent common ancestor vary according to the method used and the assumptions about the prior distributions of model parameters, but are generally consistent with other global Y chromosome studies. We explore the sensitivity of these results to assumptions about the prior distributions and the evolutionary models themselves.

    View details for PubMedID 15588495

  • Stable association between strains of Mycobacterium tuberculosis and their human host populations PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Hirsh, A. E., Tsolaki, A. G., DeRiemer, K., Feldman, M. W., Small, P. M. 2004; 101 (14): 4871-4876

    Abstract

    Mycobacterium tuberculosis is an important human pathogen in virtually every part of the world. Here we investigate whether distinct strains of M. tuberculosis infect different human populations and whether associations between host and pathogen populations are stable despite global traffic and the convergence of diverse strains of the pathogen in cosmopolitan urban centers. The recent global movement and transmission history of 100 M. tuberculosis isolates was inferred from a molecular epidemiologic study of tuberculosis that spans 12 years. Genetic relationships among these isolates were deduced from the distribution of large genomic deletions, which were identified by DNA microarray and confirmed by PCR and sequence analysis. Phylogenetic analysis of these deletions indicates that they are unique event polymorphisms and that horizontal gene transfer is extremely rare in M. tuberculosis. In conjunction with the epidemiological data, phylogenies reveal three large phylogeographic regions. A host's region of origin is predictive of the strain of tuberculosis he or she carries, and this association remains strong even when transmission takes place in a cosmopolitan urban center outside of the region of origin. Approximate dating of the time since divergence of East Asian and Philippine clades of M. tuberculosis suggests that these lineages diverged centuries ago. Thus, associations between host and pathogen populations appear to be highly stable.

    View details for DOI 10.1073/pnas.0305627101

    View details for Web of Science ID 000220761200029

    View details for PubMedID 15041743

  • What is altruism? TRENDS IN ECOLOGY & EVOLUTION Kerr, B., Godfrey-Smith, P., Feldman, M. W. 2004; 19 (3): 135-140

    Abstract

    Altruism is generally understood to be behavior that benefits others at a personal cost to the behaving individual. However, within evolutionary biology, different authors have interpreted the concept of altruism differently, leading to dissimilar predictions about the evolution of altruistic behavior. Generally, different interpretations diverge on which party receives the benefit from altruism and on how the cost of altruism is assessed. Using a simple trait-group framework, we delineate the assumptions underlying different interpretations and show how they relate to one another. We feel that a thorough examination of the connections between interpretations not only reveals why different authors have arrived at disparate conclusions about altruism, but also illuminates the conditions that are likely to favor the evolution of altruism.

    View details for DOI 10.1016/j.tree.2003.10.004

    View details for Web of Science ID 000220183800009

    View details for PubMedID 16701244

  • Cultural niche construction and the evolution of small family size THEORETICAL POPULATION BIOLOGY Ihara, Y., Feldman, M. W. 2004; 65 (1): 105-111

    Abstract

    A model of cultural niche construction with two culturally transmitted traits is examined. The frequency of individuals with a certain general predisposition, which is transmitted vertically, plays a role as the cultural background, or the cultural niche, of the population. The cultural background determines the rate of oblique, relative to vertical, transmission of another cultural trait that affects fertility of individuals. It is assumed that individuals with fewer offspring are more likely to achieve social roles that influence the succeeding generation and are therefore overrepresented as transmitters in the process of oblique transmission. Our model suggests that even a slight overrepresentation of those with fewer offspring can drive the evolution of small family size, provided that the rate of oblique transmission depends strongly on the cultural background. In addition, our model may help to explain the time lag between the decrease in death rates and the subsequent decrease in birth rates during the demographic transition of industrializing societies.

    View details for DOI 10.1016/j.tpb.2003.07.003

    View details for Web of Science ID 000187356600009

    View details for PubMedID 14642348

  • Robustness of the inference of human population structure: a comparison of X-chromosomal and autosomal microsatellites. Human genomics Ramachandran, S., Rosenberg, N. A., Zhivotovsky, L. A., Feldman, M. W. 2004; 1 (2): 87-97

    Abstract

    In this paper, data on 20 X-chromosomal microsatellite polymorphisms from the HGDP-CEPH cell line panel are used to infer human population structure. Inferences from these data are compared to those obtained from autosomal microsatellites. Some of the major features of the structure seen with 377 autosomal markers are generally visible with the X-linked markers, although the latter provide less resolution. Differences between the X-chromosomal and autosomal results can be explained without requiring major differences in demographic parameters between males and females. The dependence of the partitioning on the number of individuals sampled from each region and on the number of markers used is discussed.

    View details for PubMedID 15601537

  • Reconstruction of patrilineages and matrilineages of Samaritans and other Israeli populations from Y-chromosome and mitochondrial DNA sequence variation HUMAN MUTATION Shen, P. D., Lavi, T., Kivisild, T., Chou, V., Sengun, D., Gefel, D., Shpirer, I., Woolf, E., Hillel, J., Feldman, M. W., Oefner, P. J. 2004; 24 (3): 248-260

    Abstract

    The Samaritan community, which numbered more than a million in late Roman times and only 146 in 1917, numbers today about 640 people representing four large families. They are culturally different from both Jewish and non-Jewish populations in the Middle East and their origin remains a question of great interest. Genetic differences between the Samaritans and neighboring Jewish and non-Jewish populations are corroborated in the present study of 7,280 bp of nonrecombining Y-chromosome and 5,622 bp of coding and hypervariable segment I (HVS-I) mitochondrial DNA (mtDNA) sequences. Comparative sequence analysis was carried out on 12 Samaritan Y-chromosome, and mtDNA samples from nine male and seven female Samaritans separated by at least two generations. In addition, 18-20 male individuals were analyzed, each representing Ethiopian, Ashkenazi, Iraqi, Libyan, Moroccan, and Yemenite Jews, as well as Druze and Palestinians, all currently living in Israel. The four Samaritan families clustered to four distinct Y-chromosome haplogroups according to their patrilineal identity. Of the 16 Samaritan mtDNA samples, 14 carry either of two mitochondrial haplotypes that are rare or absent among other worldwide ethnic groups. Principal component analysis suggests a common ancestry of Samaritan and Jewish patrilineages. Most of the former may be traced back to a common ancestor in the paternally-inherited Jewish high priesthood (Cohanim) at the time of the Assyrian conquest of the kingdom of Israel.

    View details for DOI 10.1002/humu.20077

    View details for Web of Science ID 000223304800008

    View details for PubMedID 15300852

  • Evolution of disassortative and assortative mating preferences based on imprinting THEORETICAL POPULATION BIOLOGY Ihara, Y., Feldman, M. W. 2003; 64 (2): 193-200

    Abstract

    A two-locus haploid model of sexual selection is investigated to explore evolution of disassortative and assortative mating preferences based on imprinting. In this model, individuals imprint on a genetically transmitted trait during early ontogeny and choosy females later use those parental images as a criterion of mate choice. It is assumed that the presence or absence of the female preference is determined by a genetic locus. In order to incorporate such mechanisms as inbreeding depression and heterozygous advantage into our haploid framework, we assume that same-type matings are less fertile than different-type mating. The model suggests that: if all the females have a disassortative mating preference a viability-reducing trait may be maintained even without the fertility cost of same-type matings; a disassortative mating preference can be established even if it is initially rare, when there is a fertility cost of same-type matings. Further, an assortative mating preference is less likely to evolve than a disassortative mating preference. The model may be applicable to the evolution of MHC-disassortative mating preferences documented in house mice and humans.

    View details for DOI 10.1016/S0040-5809(03)00099-6

    View details for Web of Science ID 000185265500006

    View details for PubMedID 12948680

  • Rates of DNA duplication and mitochondrial DNA insertion in the human genome JOURNAL OF MOLECULAR EVOLUTION Bensasson, D., Feldman, M. W., Petrov, D. A. 2003; 57 (3): 343-354

    Abstract

    The hundreds of mitochondrial pseudogenes in the human nuclear genome sequence (numts) constitute an excellent system for studying and dating DNA duplications and insertions. These pseudogenes are associated with many complete mitochondrial genome sequences and through those with a good fossil record. By comparing individual numts with primate and other mammalian mitochondrial genome sequences, we estimate that these numts arose continuously over the last 58 million years. Our pairwise comparisons between numts suggest that most human numts arose from different mitochondrial insertion events and not by DNA duplication within the nuclear genome. The nuclear genome appears to accumulate mtDNA insertions at a rate high enough to predict within-population polymorphism for the presence/absence of many recent mtDNA insertions. Pairwise analysis of numts and their flanking DNA produces an estimate for the DNA duplication rate in humans of 2.2 x 10(-9) per numt per year. Thus, a nucleotide site is about as likely to be involved in a duplication event as it is to change by point substitution. This estimate of the rate of DNA duplication of noncoding DNA is based on sequences that are not in duplication hotspots, and is close to the rate reported for functional genes in other species.

    View details for DOI 10.1007/s00239-003-2485-7

    View details for Web of Science ID 000184992800012

    View details for PubMedID 14629044

  • Recent duplication of the, common carp (Cyprinus carpio L.) genome as revealed by analyses of microsatellite loci MOLECULAR BIOLOGY AND EVOLUTION David, L., Blum, S., Feldman, M. W., Lavi, U., Hillel, J. 2003; 20 (9): 1425-1434

    Abstract

    Genome duplications may have played a role in the early stages of vertebrate evolution, near the time of divergence of the lamprey lineage. Additional genome duplication, specifically in ray-finned fish, may have occurred before the divergence of the teleosts. The common carp (Cyprinus carpio) has been considered tetraploid because of its chromosome number (2n = 100) and its high DNA content. We studied variation using 59 microsatellite primer pairs to better understand the ploidy level of the common carp. Based on the number of PCR amplicons per individual, about 60% of these primer pairs are estimated to amplify duplicates. Segregation patterns in families suggested a partially duplicated genome structure and disomic inheritance. This could suggest that the common carp is tetraploid and that polyploidy occurred by hybridization (allotetraploidy). From sequences of microsatellite flanking regions, we estimated the difference per base between pairs of alleles and between pairs of paralogs. The distribution of differences between paralogs had two distinct modes suggesting one whole-genome duplication and a more recent wave of segmental duplications. The genome duplication was estimated to have occurred about 12 MYA, with the segmental duplications occurring between 2.3 and 6.8 MYA. At 12 MYA, this would be one of the most recent genome duplications among vertebrates. Phylogenetic analysis of several cyprinid species suggests an evolutionary model for this tetraploidization, with a role for polyploidization in speciation and diversification.

    View details for DOI 10.1093/molbev/msg173

    View details for Web of Science ID 000185175500003

    View details for PubMedID 12832638

  • A genetic melting-pot NATURE Feldman, M. W., Lewontin, R. C., KING, M. C. 2003; 424 (6947): 374-374

    View details for DOI 10.1038/424374a

    View details for Web of Science ID 000184318400020

    View details for PubMedID 12879045

  • The application of molecular genetic approaches to the study of human evolution NATURE GENETICS Cavalli-Sforza, L. L., Feldman, M. W. 2003; 33: 266-275

    Abstract

    The past decade of advances in molecular genetic technology has heralded a new era for all evolutionary studies, but especially the science of human evolution. Data on various kinds of DNA variation in human populations have rapidly accumulated. There is increasing recognition of the importance of this variation for medicine and developmental biology and for understanding the history of our species. Haploid markers from mitochondrial DNA and the Y chromosome have proven invaluable for generating a standard model for evolution of modern humans. Conclusions from earlier research on protein polymorphisms have been generally supported by more sophisticated DNA analysis. Co-evolution of genes with language and some slowly evolving cultural traits, together with the genetic evolution of commensals and parasites that have accompanied modern humans in their expansion from Africa to the other continents, supports and supplements the standard model of genetic evolution. The advances in our understanding of the evolutionary history of humans attests to the advantages of multidisciplinary research.

    View details for DOI 10.1038/ng1113

    View details for Web of Science ID 000181390900007

    View details for PubMedID 12610536

  • Extensive linkage disequilibrium, a common 16.7-kilobase deletion, and evidence of balancing selection in the human protocadherin alpha cluster AMERICAN JOURNAL OF HUMAN GENETICS Noonan, J. P., Li, J., Nguyen, L., Caoile, C., Dickson, M., Grimwood, J., Schmutz, J., Feldman, M. W., Myers, R. M. 2003; 72 (3): 621-635

    Abstract

    Regions of extensive linkage disequilibrium (LD) appear to be a common feature of the human genome. However, the mechanisms that maintain these regions are unknown. In an effort to understand whether gene density contributes to LD, we determined the degree of promoter sequence variation in a large tandem-arrayed gene family, the human protocadherin alpha cluster, on chromosome 5. These genes are expressed at synaptic junctions in the developing brain and the adult brain and may be involved in the determination of synaptic complexity. We sequenced the promoters of all 13 alpha protocadherin genes in 96 European Americans and identified polymorphisms in the promoters alpha 1, alpha 3, alpha 4, alpha 5, alpha 7, alpha 9, alpha 11, and alpha 13. In these promoters, 11 common SNPs are in extensive LD, forming two 48-kb haplotypes of equal frequency, in this population, that extend from the alpha1 through alpha 7 genes. We sequenced these promoters in East Asians and African Americans, and we estimated haplotype frequencies and calculated LD statistics for all three populations. Our results indicate that, although extensive LD is an ancient feature of the alpha cluster, it has eroded over time. SNPs 3' of alpha 7 are involved in ancestral recombination events in all populations, and overall alpha-cluster LD is reduced in African Americans. We obtained significant positive values for Tajima's D test for all alpha promoter SNPs in Europeans (D=3.03) and East Asians (D=2.64), indicating an excess of intermediate-frequency variants, which is a signature of balancing selection. We also discovered a 16.7-kb deletion that truncates the alpha 8 gene and completely removes the alpha 9 and alpha 10 genes. This deletion appears in unaffected individuals from multiple populations, suggesting that a reduction in protocadherin gene number is not obviously deleterious.

    View details for Web of Science ID 000181152600012

    View details for PubMedID 12577201

  • Runaway sexual selection with paternal transmission of the male trait and gene-culture determination of the female preference THEORETICAL POPULATION BIOLOGY Ihara, Y., Aoki, K., Feldman, M. W. 2003; 63 (1): 53-62

    Abstract

    Sexual selection is modeled with a male viability-reducing trait and a female mating preference for that trait both of which are culturally transmitted. Both the male trait and the female preference are transmitted only between same-sex individuals, so that non-random association between the trait and the preference, which would give rise to a Fisherian runaway process, cannot arise. Inclusion of an autosomal gene that confers a female predisposition to acquire a certain preference is shown to allow the coevolution of the male trait and the female preference by a Fisherian process. This holds true even when the female preference has a slight viability cost, provided the male cultural transmission is not perfect. It is also suggested that a Fisherian process can be more easily initiated in these models than in the conventional genetic models. Furthermore, a Fisherian process may cause cultural transmission of female preference to evolve. Additionally, polymorphism can be maintained at the predisposition locus if heterozygous females have a stronger predisposition to acquire the preference than homozygotes. Our models may be applicable to the case when the male trait is a Y-linked genetic or environmentally determined trait.

    View details for Web of Science ID 000180151400005

    View details for PubMedID 12464495

  • Carving the cognitive niche: Optimal learning strategies in homogeneous and heterogeneous environments JOURNAL OF THEORETICAL BIOLOGY Kerr, B., Feldman, M. W. 2003; 220 (2): 169-188

    Abstract

    A model learning system is constructed, in which an organism samples behaviors from a behavioral repertoire in response to a stimulus and selects the behavior with the highest payoff. The stimulus and most rewarding behavior may be kept in the organism's long-term memory and reused if the stimulus is encountered again. The value of the memory depends on the reliability of the stimulus, that is, how the corresponding payoffs of behaviors change over time. We describe how the inclusion of memory can increase the optimal sampling size in environments with some stimulus reliability. In addition to using memory to guide behavior, our organism may use information in its memory to choose the stimulus to which it reacts. This choice is influenced by both the organism's memory state and how many stimuli the organism can observe (its sensory capability). The number of sampled behaviors, memory length, and sensory capability are the variables that define the learning strategy. When all stimuli have the same reliability, there appears to be only a single optimal learning strategy. However, when there is heterogeneity in stimulus reliability, multiple locally optimal strategies may exist.

    View details for DOI 10.1006/jtbi.2003.3146

    View details for Web of Science ID 000181037600003

    View details for PubMedID 12468290

  • Coevolution of pathogens and cultural practices: A new look at behavioral heterogeneity in epidemics THEORETICAL POPULATION BIOLOGY Tanaka, M. M., Kumm, J., Feldman, M. W. 2002; 62 (2): 111-119

    Abstract

    The effect of heterogeneity within populations on the spread of infectious diseases has been a recent focus of research. Such heterogeneity may be, for example, spatial, temporal or behavioral in form. Generally, models that include population subdivision have assumed that individuals are permanently assigned to given behavioral states represented by the subpopulations. We consider a simple epidemic model in which a behavioral trait affects disease transmission, and this trait may be transferred among hosts as a consequence of social interaction. This creates a situation where the frequencies of different behavioral traits and disease states as well as their associations may change over time. We consider the impact of the culturally transmitted trait on the criterion for initial spread of the disease. We also explore the evolution of cultural traits in response to pathogen dynamics and show some conditions under which behavioral traits that reduce transmission evolve. We find that behaviors increasing the risk of infection can also evolve when they are inherently favored or when there is sufficient clustering of contacts between like behaviors.

    View details for DOI 10.1006/tpbi.2002.1585

    View details for Web of Science ID 000177739700002

    View details for PubMedID 12167351

  • Local dispersal promotes biodiversity in a real-life game of rock-paper-scissors NATURE Kerr, B., Riley, M. A., Feldman, M. W., Bohannan, B. J. 2002; 418 (6894): 171-174

    Abstract

    One of the central aims of ecology is to identify mechanisms that maintain biodiversity. Numerous theoretical models have shown that competing species can coexist if ecological processes such as dispersal, movement, and interaction occur over small spatial scales. In particular, this may be the case for non-transitive communities, that is, those without strict competitive hierarchies. The classic non-transitive system involves a community of three competing species satisfying a relationship similar to the children's game rock-paper-scissors, where rock crushes scissors, scissors cuts paper, and paper covers rock. Such relationships have been demonstrated in several natural systems. Some models predict that local interaction and dispersal are sufficient to ensure coexistence of all three species in such a community, whereas diversity is lost when ecological processes occur over larger scales. Here, we test these predictions empirically using a non-transitive model community containing three populations of Escherichia coli. We find that diversity is rapidly lost in our experimental community when dispersal and interaction occur over relatively large spatial scales, whereas all populations coexist when ecological processes are localized.

    View details for DOI 10.1038/nature00823

    View details for Web of Science ID 000176710400037

    View details for PubMedID 12110887

  • Frequentist estimation of coalescence times from nucleotide sequence data using a tree-based partition GENETICS Tang, H., Siegmund, D. O., Shen, P. D., Oefner, P. J., Feldman, M. W. 2002; 161 (1): 447-459

    Abstract

    This article proposes a method of estimating the time to the most recent common ancestor (TMRCA) of a sample of DNA sequences. The method is based on the molecular clock hypothesis, but avoids assumptions about population structure. Simulations show that in a wide range of situations, the point estimate has small bias and the confidence interval has at least the nominal coverage probability. We discuss conditions that can lead to biased estimates. Performance of this estimator is compared with existing methods based on the coalescence theory. The method is applied to sequences of Y chromosomes and mtDNAs to estimate the coalescent times of human male and female populations.

    View details for Web of Science ID 000175814900040

    View details for PubMedID 12019257

  • Empirical evaluation of genetic clustering methods using multilocus genotypes from 20 chicken breeds GENETICS Rosenberg, N. A., Burke, T., Elo, K., Feldmann, M. W., Freidlin, P. J., Groenen, M. A., Hillel, J., Maki-Tanila, A., Tixier-Boichard, M., Vignal, A., Wimmers, K., Weigend, S. 2001; 159 (2): 699-713

    Abstract

    We tested the utility of genetic cluster analysis in ascertaining population structure of a large data set for which population structure was previously known. Each of 600 individuals representing 20 distinct chicken breeds was genotyped for 27 microsatellite loci, and individual multilocus genotypes were used to infer genetic clusters. Individuals from each breed were inferred to belong mostly to the same cluster. The clustering success rate, measuring the fraction of individuals that were properly inferred to belong to their correct breeds, was consistently approximately 98%. When markers of highest expected heterozygosity were used, genotypes that included at least 8-10 highly variable markers from among the 27 markers genotyped also achieved >95% clustering success. When 12-15 highly variable markers and only 15-20 of the 30 individuals per breed were used, clustering success was at least 90%. We suggest that in species for which population structure is of interest, databases of multilocus genotypes at highly variable markers should be compiled. These genotypes could then be used as training samples for genetic cluster analysis and to facilitate assignments of individuals of unknown origin to populations. The clustering algorithm has potential applications in defining the within-species genetic units that are useful in problems of conservation.

    View details for Web of Science ID 000171744900023

    View details for PubMedID 11606545

  • Distinctive genetic signatures in the Libyan Jews PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Rosenberg, N. A., Woolf, E., Pritchard, J. K., Schaap, T., Gefel, D., Shpirer, I., Lavi, U., Bonne-Tamir, B., Hillel, J., Feldman, M. W. 2001; 98 (3): 858-863

    Abstract

    Unlinked autosomal microsatellites in six Jewish and two non-Jewish populations were genotyped, and the relationships among these populations were explored. Based on considerations of clustering, pairwise population differentiation, and genetic distance, we found that the Libyan Jewish group retains genetic signatures distinguishable from those of the other populations, in agreement with some historical records on the relative isolation of this community. Our methods also identified evidence of some similarity between Ethiopian and Yemenite Jews, reflecting possible migration in the Red Sea region. We suggest that high-resolution statistical methods that use individual multilocus genotypes may make it practical to distinguish related populations of extremely recent common ancestry.

    View details for Web of Science ID 000166807300021

    View details for PubMedID 11158561

  • Y chromosome sequence variation and the history of human populations NATURE GENETICS Underhill, P. A., Shen, P. D., Lin, A. A., Jin, L., Passarino, G., Yang, W. H., Kauffman, E., Bonne-Tamir, B., Bertranpetit, J., Francalacci, P., Ibrahim, M., Jenkins, T., Kidd, J. R., Mehdi, S. Q., Seielstad, M. T., WELLS, R. S., Piazza, A., Davis, R. W., Feldman, M. W., Cavalli-Sforza, L. L., Oefner, P. J. 2000; 26 (3): 358-361

    Abstract

    Binary polymorphisms associated with the non-recombining region of the human Y chromosome (NRY) preserve the paternal genetic legacy of our species that has persisted to the present, permitting inference of human evolution, population affinity and demographic history. We used denaturing high-performance liquid chromatography (DHPLC; ref. 2) to identify 160 of the 166 bi-allelic and 1 tri-allelic site that formed a parsimonious genealogy of 116 haplotypes, several of which display distinct population affinities based on the analysis of 1062 globally representative individuals. A minority of contemporary East Africans and Khoisan represent the descendants of the most ancestral patrilineages of anatomically modern humans that left Africa between 35,000 and 89,000 years ago.

    View details for Web of Science ID 000165176500029

    View details for PubMedID 11062480

  • Cultural transmission in a demographic study of sex ratio at birth in China's future THEORETICAL POPULATION BIOLOGY Li, N., Feldman, M. W., Li, S. Z. 2000; 58 (2): 161-172

    Abstract

    A decline in fertility causes an increase in the sex ratio at birth (SRB) in countries with strong son preference. What happens to the SRB if fertility is maintained at a low level depends on the evolution of son preference. In this paper, we analyze trends in son preference and its effect on China's future SRB.

    View details for Web of Science ID 000090097500006

    View details for PubMedID 11042106

  • The dynamics of repeated elements: Applications to the epidemiology of tuberculosis PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Tanaka, M. M., Small, P. M., Salamon, H., Feldman, M. W. 2000; 97 (7): 3532-3537

    Abstract

    We propose a stepwise mutation model to describe the dynamics of DNA fingerprint variation in Mycobacterium tuberculosis. The genome of M. tuberculosis carries insertion sequences (IS6110) that are relatively stable over time periods of months but have an observable transposition rate over longer time scales. Variability in copy number and genomic location of (IS6110) can be harnessed to generate a DNA fingerprint for each strain, by digesting the genome with a restriction enzyme and using a portion of the element as a probe for Southern blots. The number of bands found for a given genome approximates the number of copies of IS6110 it carries. A large data set of such fingerprints from tuberculosis (TB) cases in San Francisco provides an observed distribution of IS6110 copy number. Implementation of the model through deterministic and stochastic simulation indicates some general features of IS/TB dynamics. By comparing observations with outcomes of the model, we conclude that the IS/TB system is very heterogeneous and far from equilibrium. We find that the transposition parameters have a much stronger effect than the epidemic parameters on copy number distribution.

    View details for Web of Science ID 000086195200103

    View details for PubMedID 10716736

  • Population growth of human Y chromosomes: A study of Y chromosome microsatellites MOLECULAR BIOLOGY AND EVOLUTION Pritchard, J. K., Seielstad, M. T., Perez-Lezaun, A., Feldman, M. W. 1999; 16 (12): 1791-1798

    Abstract

    We use variation at a set of eight human Y chromosome microsatellite loci to investigate the demographic history of the Y chromosome. Instead of assuming a population of constant size, as in most of the previous work on the Y chromosome, we consider a model which permits a period of recent population growth. We show that for most of the populations in our sample this model fits the data far better than a model with no growth. We estimate the demographic parameters of this model for each population and also the time to the most recent common ancestor. Since there is some uncertainty about the details of the microsatellite mutation process, we consider several plausible mutation schemes and estimate the variance in mutation size simultaneously with the demographic parameters of interest. Our finding of a recent common ancestor (probably in the last 120,000 years), coupled with a strong signal of demographic expansion in all populations, suggests either a recent human expansion from a small ancestral population, or natural selection acting on the Y chromosome.

    View details for Web of Science ID 000084147700014

    View details for PubMedID 10605120

  • Theoretical considerations of cross-immunity, recombination and the evolution of new parasitic strains JOURNAL OF THEORETICAL BIOLOGY Tanaka, M. M., Feldman, M. W. 1999; 198 (2): 145-163

    Abstract

    We explore the dynamics of multiple strains of a parasite in order to assess the conditions under which a novel strain, perhaps a mutant or migrant, may invade a population that already carries an endemic strain. Multiple strain dynamics can be modeled through coinfection or complete cross-immunity. We examine these three modes to discuss the relationships among cross-immunity, the basic reproductive rates of each strain, and the invasion of the new strain. Superinfection is more restrictive than coinfection in the proportion of parameters that allows invasion. The coinfection model is extended to allow haploid strains to undergo recombination within the host. We investigate the effects of recombination and cross-immunity on the invasion of new strains. Interestingly, although recombination is understood to generate diversity, it is not always advantageous.

    View details for Web of Science ID 000080543300001

    View details for PubMedID 10339390

  • Gene-culture coevolution and sex ratios .2. Sex-chromosomal distorters and cultural preferences for offspring sex THEORETICAL POPULATION BIOLOGY Kumm, J., Feldman, M. W. 1997; 52 (1): 1-15

    Abstract

    Cultural preferences for the sex of offspring may produce behavior, such as female infanticide, sex-selective abortion and sex-selective parental investment, which alter the sex ratio in a population. Empirical evidence suggests that some genetic sex-ratio distorters are located on the sex chromosomes. Interactions between cultural preferences and sex-linked sex-ratio distorters are examined. Criteria for the spread of cultural preferences and sex-chromosomal distorter alleles are derived analytically, and the coevolution of preferences and distorters is examined through numerical iteration. Evolutionary equilibria and trajectories of gene-culture interactions involving sex-chromosomal distorter alleles may produce severely male- or female-biased primary sex ratios and adult sex ratios in populations. Adult sex ratios, primary sex ratios, allele frequencies and the prevalence of cultural preferences in the population are sensitive to initial conditions and cultural transmission parameters. During the coevolutionary process phenoallelic association is observed in many cases and is associated with unusual dynamics.

    View details for Web of Science ID A1997YA85000001

    View details for PubMedID 9345791

  • Microsatellite genetic distances with range constraints: Analytic description and problems of estimation GENETICS Feldman, M. W., Bergman, A., Pollock, D. D., Goldstein, D. B. 1997; 145 (1): 207-216

    Abstract

    Statistical properties of the symmetric stepwise-mutation model for microsatellite evolution are studied under the assumption that the number of repeats is strictly bounded above and below. An exact analytic expression is found for the expected products of the frequencies of alleles separated by k repeats. This permits characterization of the asymptotic behavior of our distances D1 and (delta mu)2 under range constraints. Based on this characterization we develop transformations that partially restore linearity when allele size is restricted. We show that the appropriate transformation cannot be applied in the case of varying mutation rates (beta) and range constraints (R) because of statistical difficulties. In the special case of no variation in beta and R across loci, however, the transformation simplifies to a usable form and results in a distance much more linear with time than distances developed for an infinite range. Although analytically incorrect in the case of variation in beta and R, the simpler transformation is surprisingly insensitive to variation in these parameters, suggesting that it may have considerable utility in phylogenetic studies.

    View details for Web of Science ID A1997WC86800021

    View details for PubMedID 9017402

  • Gene-Culture Coevolution and Sex Ratios: II. Sex-Chromosomal Distorters and Cultural Preferences for Offspring Sex Theoretical population biology Kumm, J., Feldman, M. W. 1997; 7 (1): 1-15

    Abstract

    Cultural preferences for the sex of offspring may produce behavior, such as female infanticide, sex-selective abortion and sex-selective parental investment, which alter the sex ratio in a population. Empirical evidence suggests that some genetic sex-ratio distorters are located on the sex chromosomes. Interactions between cultural preferences and sex-linked sex-ratio distorters are examined. Criteria for the spread of cultural preferences and sex-chromosomal distorter alleles are derived analytically, and the coevolution of preferences and distorters is examined through numerical iteration. Evolutionary equilibria and trajectories of gene-culture interactions involving sex-chromosomal distorter alleles may produce severely male- or female-biased primary sex ratios and adult sex ratios in populations. Adult sex ratios, primary sex ratios, allele frequencies and the prevalence of cultural preferences in the population are sensitive to initial conditions and cultural transmission parameters. During the coevolutionary process phenoallelic association is observed in many cases and is associated with unusual dynamics. Copyright 1997 Academic Press

    View details for PubMedID 9356319

  • Statistics for microsatellite variation based on coalescence THEORETICAL POPULATION BIOLOGY Pritchard, J. K., Feldman, M. W. 1996; 50 (3): 325-344

    Abstract

    The stepwise mutation model, which was at one time chiefly of interest in studying the evolution of protein charge-states, has recently undergone a resurgence of interest with the new popularity of microsatellites as phylogenetic markers. In this paper we describe a method which makes it possible to transfer many population genetics results from the standard infinite sites model to the stepwise mutation model. We study in detail the properties of pairwise differences in microsatellite repeat number between randomly chosen alleles. We show that the problem of finding the expected squared distance between two individuals and finding the variance of the squared distance can be reduced for a wide range of population models to finding the mean and mean square coalescence times. In many cases the distributions of coalescence times have already been studied for infinite site problems. In this study we show how to calculate these quantities for several population models. We also calculate the variance in mean squared pairwise distance (an estimator of mutation rate x population size) for samples of arbitrary size and show that this variance does not approach zero as the sample size increases. We can also use our method to study alleles at linked microsatellite loci. We suggest a metric which quantifies the level of association between loci-effectively a measure of linkage disequilibrium. It is shown that there can be linkage disequilibrium between partially linked loci at mutation-drift equilibrium.

    View details for Web of Science ID A1996WA54400006

    View details for PubMedID 9000493

  • Fitness patterns and phenotypic plasticity in a spatially heterogeneous environment GENETICAL RESEARCH Zhivotovsky, L. A., Feldman, M. W., Bergman, A. 1996; 68 (3): 241-248

    Abstract

    We analyse patterns of the means and variances of genotypic fitnesses across different niches in a randomly mating haploid population. The population inhabits a spatially heterogeneous environment where it is subject to mutation and weak multilocus additive selection, with different election coefficients in different niches. Approximate analytical expressions are derived for the stationary mean and variance of genotypic fitnesses among the niches in terms of environmental and genetic parameters. As a special case, we analyse an environment described by a variable t, distributed among the niches with mean t(star) and variance D(star) and quadratic decrease in correlation between environments as a function of the difference in values of t. If the niches have the same qualities, the mean and variance of genotypic fitnesses evolve to be quadratic functions of t that achieve their maximum and minimum, respectively, at t(star). With unequal niche qualities, these are non-polynomial functions that attain their extrema at different, usually intermediate values of t, although the coefficient of variation of the genotypic fitnesses still attains its minimum near t(star). The functions involve the total mutation rate, the combination of the loci to genotypic fitnesses, and the frequency and quality distributions of the niches. Thus, for this relatively simple model the norms of reaction may be calculated in terms of the detailed properties of the environmental heterogeneity, and the genetic system.

    View details for Web of Science ID A1996WN32200006

    View details for PubMedID 9062081

  • Statistical properties of the variation at linked microsatellite loci: Implications for the history of human Y chromosomes MOLECULAR BIOLOGY AND EVOLUTION Goldstein, D. B., Zhivotovsky, L. A., Nayar, K., Linares, A. R., CAVALLISFORZA, L. L., Feldman, M. W. 1996; 13 (9): 1213-1218

    Abstract

    It has recently been suggested that observed levels of variation at microsatellite loci can be used to infer patterns of selection in genomes and to assess demographic history. In order to evaluate the feasibility of these suggestions it is necessary to know something about how levels of variation at microsatellite loci are expected to fluctuate due simply to stochasticity in the processes of mutation and inheritance (genetic sampling). Here we use recently derived properties of the stepwise mutation model to place confidence intervals around the variance in repeat score that is expected at mutation-drift equilibrium and outline a statistical test for whether an observed value differs significantly from expectation. We also develop confidence intervals for the time course of the buildup of variation following a complete elimination of variation, such as might be caused by a selective sweep or an extreme population bottleneck. We apply these methods to the variation observed at human Y-specific microsatellites. Although a number of authors have suggested the possibility of a very recent sweep, our analyses suggest that a sweep or extreme bottleneck is unlikely to have occurred anytime during the last approximately 74,000 years. To generate this result we use a recently estimated mutation rate for microsatellite loci of 5.6 x 10(-4) along with the variation observed at autosomal microsatellite loci to estimate the human effective population size. This estimate is 18,000, implying an effective number of 4,500 Y chromosomes. One important general conclusion to emerge from this study is that in order to reject mutation-drift equilibrium at a set of linked microsatellite loci it is necessary to have an unreasonably large number of loci unless the observed variance is far below that expected at mutation-drift equilibrium.

    View details for Web of Science ID A1996VR29900007

    View details for PubMedID 8896373

  • Gene-culture coevolutionary theory TRENDS IN ECOLOGY & EVOLUTION Feldman, M. W., Laland, K. N. 1996; 11 (11): 453-457

    Abstract

    Gene-culture coevolutionary theory is a branch of theoretical population genetics that models the transmission of genes and cultural traits from one generation to the next, exploring how they interact. These models have been employed to examine the adaptive advantages of learning and culture, to investigate the forces of cultural change, to partition the variance in complex human behavioral and personality traits, and to address specific cases in human evolution in which there is an interaction between genes and culture.

    View details for Web of Science ID A1996VN15900006

    View details for PubMedID 21237920

  • Geographic clustering of human Y-chromosome haplotypes. Annals of human genetics Ruiz Linares, A., Nayar, K., Goldstein, D. B., Hebert, J. M., Seielstad, M. T., Underhill, P. A., Lin, A. A., Feldman, M. W., Cavalli Sforza, L. L. 1996; 60: 401-408

    Abstract

    Five polymorphic markers on the Y-chromosome (mostly microsatellites) were typed in 121 individuals from 13 populations around the world. With these markers 78 different haplotypes were detected. Haplotypes present more than once tend to be shared by individuals from the same population or continent. A reconstruction of haplotype phylogeny also indicates significant geographic structure in the data. Based on the similarity of the haplotypes, population relationships were examined and found to be largely concordant with those obtained with other markers. Even though the sample size and the number of markers are small, there is very signficant clustering of the haplotypes by continent of origin.

    View details for PubMedID 8912793

  • On the evolution of phenotypic plasticity in a spatially heterogeneous environment EVOLUTION Zhivotovsky, L. A., Feldman, M. W., Bergman, A. 1996; 50 (2): 547-558
  • Population genetic perspectives on the evolution of recombination ANNUAL REVIEW OF GENETICS Feldman, M. W., Otto, S. P., Christiansen, F. B. 1996; 30: 261-295

    Abstract

    Optimality arguments and modifier theory are reviewed as paradigms for the study of the evolution of recombination. Optimality criteria (such as maximization of mean fitness) may agree with results from models developed in terms of the evolution of recombination at modifier loci. Modifier models demonstrate, however, that equilibrium mean fitness can decrease during the evolution of recombination rates and is not always maximized. Therefore, optimality arguments do not successfully predict the conditions under which increased or decreased recombination will evolve. The results from modifier models indicate that decreased recombination rates are usually favored when the population is initially near a polymorphic equilibrium with linkage disequilibrium. When the population is subject to directional selection or to deleterious mutations, increased recombination may be favored under certain conditions, provided that there is negative epistasis among alleles.

    View details for Web of Science ID A1996WA81200011

    View details for PubMedID 8982456

  • MICROSATELLITE VARIABILITY AND GENETIC DISTANCES PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Zhivotovsky, L. A., Feldman, M. W. 1995; 92 (25): 11549-11552

    Abstract

    We analyze the within- and between-population dynamics of the distribution of the number of repeats at multiple microsatellite DNA loci subject to stepwise mutation. Analytical expressions for moments up to the fourth order within a locus and the variance of between-locus variance at mutation-drift equilibrium have been obtained. These statistics may be used to test the appropriateness of the one-step mutation model and to detect between-locus variation in the mutation rate. Published data are compatible with the one-step mutation model, although they do not reject the two-step model. Using both multinomial sampling and diffusion approximations for the analysis of the genetic distance introduced by Goldstein et al. [Goldstein, D. B., Linares, A. R., Cavalli-Sforza, L. L. & Feldman, M. W. (1995) Proc. Natl. Acad. Sci. USA 92, 6723-6727], we show that this distance follows a chi 2 distribution with degrees of freedom equal to the number of loci when there is no variation in mutation rates among the loci. In the presence of such variation, the variance of the distance is obtained. We conclude that the number of microsatellite loci required for the construction of phylogenetic trees with reliable branch lengths may be several hundred. Also, mutations that change repeat scores by several units, even though extremely rare, may dramatically influence estimates of population parameters.

    View details for Web of Science ID A1995TJ22200048

    View details for PubMedID 8524801

  • A GENE-CULTURE MODEL OF HUMAN HANDEDNESS BEHAVIOR GENETICS Laland, K. N., Kumm, J., VanHorn, J. D., Feldman, M. W. 1995; 25 (5): 433-445

    Abstract

    A model of handedness incorporating both genetic and cultural processes is proposed, based on an evolutionary analysis, and maximum-likelihood estimates of its parameters are generated. This model has the characteristics that (i) no genetic variation underlies variation in handedness, and (ii) variation in handedness among humans is the result of a combination of cultural and developmental factors, but (iii) a genetic influence remains since handedness is a facultative trait. The model fits the data from 17 studies of handedness in families and 14 studies of handedness in monozygotic and dizygotic twins. This model has the additional advantages that it can explain why monozygotic and dizygotic twins and siblings have similar concordance rates, and no hypothetical selection regimes are required to explain the persistence of left handedness.

    View details for Web of Science ID A1995RW36200003

    View details for PubMedID 7487840

  • GENETIC ABSOLUTE DATING BASED ON MICROSATELLITES AND THE ORIGIN OF MODERN HUMANS PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Goldstein, D. B., Linares, A. R., CAVALLISFORZA, L. L., Feldman, M. W. 1995; 92 (15): 6723-6727

    Abstract

    We introduce a new genetic distance for microsatellite loci, incorporating features of the stepwise mutation model, and test its performance on microsatellite polymorphisms in humans, chimpanzees, and gorillas. We find that it performs well in determining the relations among the primates, but less well than other distance measures (not based on the stepwise mutation model) in determining the relations among closely related human populations. However, the deepest split in the human phylogeny seems to be accurately reconstructed by the new distance and separates African and non-African populations. The new distance is independent of population size and therefore allows direct estimation of divergence times if the mutation rate is known. Based on 30 microsatellite polymorphisms and a recently reported average mutation rate of 5.6 x 10(-4) at 15 dinucleotide microsatellites, we estimate that the deepest split in the human phylogeny occurred about 156,000 years ago. Unlike most previous estimates, ours requires no external calibration of the rate of molecular evolution. We can use such calibrations, however, to test our estimate.

    View details for Web of Science ID A1995RJ89200012

    View details for PubMedID 7624310

  • EFFECTS OF CIS-TRANS VIABILITY SELECTION ON SOME 2-LOCUS MODELS THEORETICAL POPULATION BIOLOGY Nordborg, M., Franklin, I. R., Feldman, M. W. 1995; 47 (3): 365-392

    Abstract

    Most analyses of two-locus viability models have assumed that the fitness of double heterozygotes are the same whether in the cis or trans configuration. This assumption is unlikely to hold for polymorphic sites within the same locus. We examine the quantitative and qualitative effects of incorporating cis-trans viability differences into a number of deterministic two-locus models. A new result is the finding that two asymmetric equilibria with similar levels of linkage disequilibrium, but different gene frequencies, may arise in quite realistic biological models. The general, and most important, conclusion is that high levels of linkage disequilibrium may be generated by very small selective differences in cis and trans. Polymorphic sites that interact selectively are expected to show high levels of linkage disequilibrium. Conversely, if two polymorphic sites within a gene are found to be in linkage equilibrium, it is likely that one or both are selectively neutral.

    View details for Web of Science ID A1995RL20900007

    View details for PubMedID 7667795

  • THE REDUCTION PRINCIPLE FOR RECOMBINATION UNDER DENSITY-DEPENDENT SELECTION THEORETICAL POPULATION BIOLOGY Zhivotovsky, L. A., Feldman, M. W. 1995; 47 (2): 244-256

    Abstract

    In diploid random mating populations with constant viability selection, genetic modifiers of recombination, introduced near equilibria that exhibit genetic association, invade if they reduce recombination. In this study we combine ecological and standard populations genetics in a haploid multilocus model that includes density-dependent regulation of population size and weak density-dependent differential selection among the multilocus genotypes. An allele that affects recombination among the genes contributing to the ecological selection, introduced near a stable equilibrium of the ecological-genetic system, invades if it reduces a weighted average of the recombination rates among pairs of loci under selection. This generalizes the Reduction Principle for the evolution of recombination (M. W. Feldman and U. Liberman, Proc. Nat. Acad. Sci. USA 83, 4824-4827, 1986; L. A. Zhivotovsky, W. M. Feldman, and F. B. Christiansen, Theor. Popul. Biol. 44, 225-245, 1993). It is also shown that the stronger the extent of density-dependence, the weaker the selection for reduced recombination.

    View details for Web of Science ID A1995QR83000005

    View details for PubMedID 7740441

  • HIGH SEX-RATIOS IN CHINA FUTURE SCIENCE Tuljapurkar, S., Li, N., Feldman, M. W. 1995; 267 (5199): 874-876

    Abstract

    In China in recent years, male live births have exceeded those of females by amounts far greater than those that occur naturally in human populations, a trend with significant demographic consequences. The resulting imbalance in the first-marriage market is estimated to be about 1 million males per year after 2010. These "excess" males were not easily accommodated in models with substantial changes in first-marriage patterns. The current sex ratio at birth has little effect on a couple's probability of having at least one son, so future increases in the sex ratio may well occur, especially given increasing access to sex-selective abortion.

    View details for Web of Science ID A1995QG20700055

    View details for PubMedID 7846529

  • GENE-CULTURE COEVOLUTIONARY THEORY - A TEST-CASE CURRENT ANTHROPOLOGY Laland, K. N., Kumm, J., Feldman, M. W. 1995; 36 (1): 131-156
  • AN EVALUATION OF GENETIC DISTANCES FOR USE WITH MICROSATELLITE LOCI GENETICS Goldstein, D. B., Linares, A. R., CAVALLISFORZA, L. L., Feldman, M. W. 1995; 139 (1): 463-471

    Abstract

    Mutations of alleles at microsatellite loci tend to result in alleles with repeat scores similar to those of the alleles from which they were derived. Therefore the difference in repeat score between alleles carries information about the amount of time that has passed since they shared a common ancestral allele. This information is ignored by genetic distances based on the infinite alleles model. Here we develop a genetic distance based on the stepwise mutation model that includes allelic repeat score. We adapt earlier treatments of the stepwise mutation model to show analytically that the expectation of this distance is a linear function of time. We then use computer simulations to evaluate the overall reliability of this distance and to compare it with allele sharing and Nei's distance. We find that no distance is uniformly superior for all purposes, but that for phylogenetic reconstruction of taxa that are sufficiently diverged, our new distance is preferable.

    View details for Web of Science ID A1995PZ24800040

    View details for PubMedID 7705647

  • GENE-CULTURE COEVOLUTION AND SEX-RATIOS - THE EFFECTS OF INFANTICIDE, SEX-SELECTIVE ABORTION, SEX SELECTION, AND SEX-BIASED PARENTAL INVESTMENT ON THE EVOLUTION OF SEX-RATIOS THEORETICAL POPULATION BIOLOGY Kumm, J., Laland, K. N., Feldman, M. W. 1994; 46 (3): 249-278

    Abstract

    The evolutionary consequences of culturally transmitted practices that cause differential mortality between the sexes, thereby distorting the sex ratio (e.g., female infanticide and sex-selective abortion), are explored using dynamic models of gene-culture coevolution. We investigate how a preference for the sex of offspring may affect the selection of genes distorting the primary sex ratio. Sex-dependent differences in mortality have been predicted to select for a male- or female-biased primary sex ratio, to have no effect, or to favor either under different circumstances. We find that when a mating pair's behavior modifies mortality rates in favor of one sex, but does not change the number of offspring produced in the mating, the primary sex ratio will evolve a bias against the favored sex. However, when the total number of offspring of a mating pair is significantly reduced as a consequence of their prejudice, the primary sex ratio will evolve to favor the preferred sex. These results hold irrespective of whether the sex ratio is distorted by the mother's, the father's or the individual's own autosomal genes. The use of dynamic models of gene-culture coevolution allows us to explore the evolution of alleles which distort the sex ratio, as well as the final equilibrium states of the system. Gene-culture interactions can provide equilibria different from those in purely genetic systems, slow the approach to these equilibria by orders of magnitude, and move the primary (PSR) and the adult sex ratio (ASR) away from any stable equilibrium for hundreds of generations.

    View details for Web of Science ID A1994PX20800001

    View details for PubMedID 7846643

  • EVOLUTION OF RECOMBINATION AMONG MULTIPLE SELECTED LOCI - A GENERALIZED REDUCTION PRINCIPLE PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Zhivotovsky, L. A., Feldman, M. W., Christiansen, F. B. 1994; 91 (3): 1079-1083

    Abstract

    Conditions for invasion by a new allele that controls the recombination pattern among an arbitrary number of genes under viability selection are studied. The recombination pattern may include interference. The new allele increases if its appropriately averaged marginal fitness is greater than the mean fitness prior to its introduction. Under weak additive-by-additive epistatic selection, this condition involves a weighted average of the changes in pairwise recombination rates relative to those prior to the introduction of the modifier. The weights here are positive functions of the epistatic selection components. In particular, the modifier allele may succeed even if it increases recombination among some pairs of loci, provided the overall average effect is one of reduction.

    View details for Web of Science ID A1994MV27800053

    View details for PubMedID 8302835

  • THE EVOLUTION OF INTERFERENCE - REDUCTION OF RECOMBINATION AMONG 3 LOCI THEORETICAL POPULATION BIOLOGY Goldstein, D. B., Bergman, A., Feldman, M. W. 1993; 44 (2): 246-259

    Abstract

    Crossover events along chromosomes do not occur independently, but influence the probability of other nearby events. The most common interaction between nearby crossover events is inhibitory: a crossover event tends to reduce the probability of other such events nearby, and this is called positive interference. A crossover event may increase the probability of events nearby, and this rare phenomenon is called negative interference. In this paper, we use numerical methods to investigate how interference among three loci would evolve if it were under the genetic control of a fourth, selectively neutral locus. We first discuss the effect of interference on the overall rate of recombination among the three loci, and then show that, under a variety of conditions, interference evolves in the same way as would be predicted based upon its effect on the overall rate of recombination. That is, the overall rate evolves in the same direction as would the rate at a locus that controls recombination between two loci directly. We then check for the existence of viability-analogous Hardy-Weinberg equilibria in the four-locus model of interference modification.

    View details for Web of Science ID A1993MB63300007

    View details for PubMedID 8248888

  • HETEROGENEOUS SELECTION IN SUBDIVIDED POPULATIONS JOURNAL OF MATHEMATICAL BIOLOGY Zhivotovsky, L. A., Feldman, M. W. 1993; 31 (7): 747-759

    Abstract

    The dynamics of allele frequencies changing under migration and heterogeneous selection in a subdivided population are investigated. Using perturbation techniques, a stationary state is obtained when migration and selection are both small. Heterogeneous selection leads to a positive correlation between values of F-statistics and heterozygosities when these are compared among sets of subdivided populations. This contrast with a negative value of the correlation obtained under Wright's classical model of homogeneous selection, and with the absence of correlation in the completely neutral situation.

    View details for Web of Science ID A1993LY30200006

    View details for PubMedID 8245733

  • ON THE PROBABILITY OF LOSS OF NEW MUTATIONS IN THE PRESENCE OF LINKAGE DISEQUILIBRIUM JOURNAL OF MATHEMATICAL BIOLOGY Zhivotovsky, L. A., Feldman, M. W. 1993; 31 (2): 177-188

    Abstract

    A new selectively neutral mutation occurs in a multilocus genetic background that has achieved a stable equilibrium at which there is a linkage disequilibrium. Perturbation techniques are applied to an extension of the branching process formulation of Fisher in order to address the question of extinction probabilities. We show that under appropriate conditions the probability of extinction of the new mutant is increased by the existence of linkage disequilibrium in the genetic background.

    View details for Web of Science ID A1993KH93600006

    View details for PubMedID 8445349

  • GENE CULTURE COEVOLUTION - TOWARD A GENERAL-THEORY OF VERTICAL TRANSMISSION PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Feldman, M. W., Zhivotovsky, L. A. 1992; 89 (24): 11935-11938

    Abstract

    A general formulation of cultural and genetic transmission is developed. The cultural transmission is vertical and the genetics may involve multiple loci. Each individual is represented by a phenogenotype, and conditions are given under which the evolutionary dynamics of phenogenotype frequencies are reducible to phenogametic or phenoallelic frequencies. The interaction between genes and culture is specified by an association measure, and results on the order of magnitude of this association at equilibrium are presented.

    View details for Web of Science ID A1992KC84400061

    View details for PubMedID 1465422

  • ASSORTATIVE MATING AND GRANDPARENTAL TRANSMISSION FACILITATE THE PERSISTENCE OF A SIGN LANGUAGE THEORETICAL POPULATION BIOLOGY Feldman, M. W., Aoki, K. 1992; 42 (2): 107-116

    Abstract

    Conditions for the persistence (i.e., protection from loss) of a sign language are investigated assuming monogenic recessive inheritance of deafness, assortative mating for deafness or hearing, and cultural transmission of the sign language to deaf individuals from their deaf parents and deaf maternal grandparents. A new method is introduced to deal with the problem of grandparental transmission in which the basic variables are the frequencies of triplets comprising a mother, a father, and their daughter of permissible phenogenotypes. Usual stability analysis is then done on the system of linear recursions in the frequencies of these triplets, derived on the assumption that signers (users of the sign language) are rare. It is shown that assortative mating is the most important factor contributing to persistence, but that grandparental transmission can also have a significant effect when assortment is as strong as observed in England and the United States.

    View details for Web of Science ID A1992JZ81400001

    View details for PubMedID 1481169

  • ON MODELS OF QUANTITATIVE GENETIC-VARIABILITY - A STABILIZING SELECTION-BALANCE MODEL GENETICS Zhivotovsky, L. A., Feldman, M. W. 1992; 130 (4): 947-955

    Abstract

    A model of stabilizing selection on a multilocus character is proposed that allows the maintenance of stable allelic polymorphism and linkage disequilibrium. The model is a generalization of Lerner's model of homeostasis in which heterozygotes are less susceptible to environmental variation and hence are superior to homozygotes under phenotypic stabilizing selection. The analysis is carried out for weak selection with a quadratic-deviation model for the stabilizing selection. The stationary state is characterized by unequal allele frequencies, unequal proportions of complementary gametes, and a reduction of the genetic (and phenotypic) variance by the linkage disequilibrium. The model is compared with Mather's polygenic balance theory, with models that include mutation-selection balance, and others that have been proposed to study the role of linkage disequilibrium in quantitative inheritance.

    View details for Web of Science ID A1992HL49000023

    View details for PubMedID 1582569

  • LEWONTIN AND KOJIMA MEET FISHER - LINKAGE IN A SYMMETRICAL MODEL OF SEX DETERMINATION GENETICS Feldman, M. W., Christiansen, F. B., Otto, S. P. 1991; 129 (1): 297-312

    Abstract

    The effect of linkage and epistasis on the evolution of the sex-ratio is studied in a symmetric two-locus model of autosomal sex determination closely related to the symmetric viability model of R. C. Lewontin and K. Kojima. R. A. Fisher's expectation of an even sex ratio for autosomal sex determination by a single gene governs the dynamics when the loci are tightly linked. However, recombination may preclude optimization of the sex ratio just as occurs in viability selection models. Many of the evolutionary phenomena known for the symmetric viability model also occur here. In addition, we exhibit a series of new phenomena related to the presence of surfaces of even sex ratio.

    View details for Web of Science ID A1991GD51200028

    View details for PubMedID 1936963

  • MUTATION MODIFICATION WITH MULTIPLICATIVE FERTILITY SELECTION THEORETICAL POPULATION BIOLOGY TWOMEY, M. J., Feldman, M. W. 1990; 37 (2): 320-342

    Abstract

    Two diallelic loci in an infinite panmictic population of diploid individuals are modelled. The A/a locus is subject to unidirectional mutation and either multiplicative fertility selection or, equivalently, sex-asymmetric viability selection. The M/m locus acts as a selectively neutral modifier of the mutation rate at A/a. The loci recombine at rate R. If the M/m locus is initially monomorphic, and the A/a locus has reached equilibrium, the fate of a new modifier allele is found to depend not just on its relative effect on mutation but also upon the linkage, R. Each initial equilibrium may be characterized by a critical value of the recombination rate, R*. If 0 less than R* less than 0.5, a sufficiently small "down" modifier of the mutation rate will invade the population when R less than R* whereas a sufficiently small "up" modifier will succeed when R greater than R*. If R* less than 0 or R* greater than 0.5, only mutation reduction may occur. Numerical analysis of 56,000 sample equilibria indicates that mutation rates may be increased, but only when the selection regime is such that the A/a locus would remain polymorphic in the absence of mutation.

    View details for Web of Science ID A1990DA37800003

    View details for PubMedID 2336642

  • 2-LOCUS AUTOSOMAL SEX DETERMINATION - ON THE EVOLUTIONARY GENETIC STABILITY OF THE EVEN SEX-RATIO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Liberman, U., Feldman, M. W., Eshel, I., Otto, S. P. 1990; 87 (5): 2013-2017

    Abstract

    In two-locus models of sex determination, there are two kinds of interior (polymorphic) equilibria. One class has the even sex ratio, and the other has equal allele frequencies in the two sexes. Equilibria of the second class may exhibit linkage disequilibrium. The condition for external stability of these second-class equilibria to invasion by a new allele is that the appropriately averaged sex ratio near the equilibrium be moved closer to the even sex ratio than the average among the resident genotypes. However, invasion by a new chromosome depends on the recombination fraction in a way that appears to preclude general results about the evolutionary genetic stability of the even sex ratio in this situation.

    View details for Web of Science ID A1990CR82000081

    View details for PubMedID 2308959

  • SPATIAL SUBDIVISION OF POPULATIONS AND ESTIMATES OF GENETIC-VARIATION THEORETICAL POPULATION BIOLOGY CAVALLISFORZA, L. L., Feldman, M. W. 1990; 37 (1): 3-25

    Abstract

    Measures of variation in space are strongly affected by correlations between subdivisions used for sampling. Here we consider variation in gene frequencies across populations. Usually the variance of gene frequencies is standardized by dividing it by the mean gene frequency times one minus the mean (FST). Under the model of isolation by distance (usually called the "stepping stone" model), at the stationary state the correlation between the gene frequencies of two populations falls exponentially with the geographic distance between them. Using this model, we derive formulas for variances of blocks of populations of different sizes in one- and two-dimensional space and suggest that the theoretical results may be useful for understanding real observations, some examples of which are presented. We demonstrate how FST increases with the degree of subdivision among populations. We also show the effect of gaps between the sampled populations. Our results are valid, however, for traits other than gene frequencies, as long as their correlation with geographic distance falls exponentially. In the extension to 2-dimensional spaces, we present in closed form the distributions of distances between nodes of a lattice or of two lattices. These distributions might have applications in ecology.

    View details for Web of Science ID A1990CU08800001

    View details for PubMedID 2326767

  • MORE ON RECOMBINATION AND SELECTION IN THE MODIFIER THEORY OF SEX-RATIO DISTORTION THEORETICAL POPULATION BIOLOGY Feldman, M. W., Otto, S. P. 1989; 35 (2): 207-225

    Abstract

    G. Maffi and S.D. Jayakar suggested a model for the two-locus control of sex determination in the mosquito Aedes aegypti (1981, Theor. Pop. Biol. 19, 19-36). This model was extended to multiple alleles and analyzed in mathematical detail by S. Lessard (1987, Theor. Pop. Biol. 31, 339-358). The model supposes that males are "Mm" and females "mm" but the transmission from males is controlled by a second gene with alleles Ai. We show that in addition to the equilibrium in which mAi in females, MAi from males and mAi from males all have the same frequencies, a second class of polymorphic equilibria exists and can be stable. The former class was shown by Lessard to be stable for intermediate and/or loose linkage. The new class of equilibria may be stable for tight linkage under the conditions that preclude stability of the former. We also develop the theory of linkage modification from the neighborhood of the new equilibrium. Successful modifiers of recombination may either reduce or increase the recombination fraction with the outcome depending on the linkage of the modifier to the major genes.

    View details for Web of Science ID A1989U629800006

    View details for PubMedID 2727954

  • A GENERAL ASYMPTOTIC PROPERTY OF 2-LOCUS SELECTION MODELS THEORETICAL POPULATION BIOLOGY Lewontin, R. C., Feldman, M. W. 1988; 34 (2): 177-193

    Abstract

    It is shown that any two-locus, two-allele model of selection with constant fitnesses has at least one polymorphic equilibrium for which the linkage association measure, D, is arbitrarily close to zero for large enough recombination, R. As R----+/- infinity, D----0 in such a way that the product l = RD----a non-zero finite constant. There may be 1, 3, or 5 distinct asymptotic equilibria, depending upon fitness parameters.

    View details for Web of Science ID A1988Q567400006

    View details for PubMedID 3232120

  • KIN SELECTION AND THE EVOLUTION OF MONOGAMY SCIENCE Peck, J. R., Feldman, M. W. 1988; 240 (4859): 1672-1674

    Abstract

    A two-locus genetic model is studied in which one locus controls the tendency of individuals to act altruistically toward siblings and the other locus controls the mating habits of females. It is demonstrated that genetic variation at the altruism locus is often sufficient to induce an increase in the frequency of genes that cause females to produce all of their offspring with a single mate. This occurs because of nonrandom associations that develop between genes that cause altruism and those that affect female mating behavior. The results provide a new explanation for the evolution of monogamy, and they suggest a previously unexplored mechanism for the evolution of a variety of other behavioral traits as well.

    View details for Web of Science ID A1988N833700036

    View details for PubMedID 3381088

  • BEHAVIOR-DEPENDENT CONTEXTS FOR REPEATED PLAYS OF THE PRISONERS-DILEMMA .2. DYNAMIC ASPECTS OF THE EVOLUTION OF COOPERATION JOURNAL OF THEORETICAL BIOLOGY Feldman, M. W., THOMAS, E. A. 1987; 128 (3): 297-315

    Abstract

    Iterated Prisoner's Dilemma models are proposed in which, at any trial, the probability of staying in the game depends on the outcome of the previous trial. If a player's choice depends on its own play (cooperate or defect) at the previous trial, it becomes possible for cooperative strategies to increase when rare in a population of egoists. A dynamic analysis is used to demonstrate that stable polymorphisms may result, and may involve more strategies than just Tit-for-Tat and all-Defect. The tendency for clustering among like strategists to enhance their initial increase when rare is also explored dynamically.

    View details for Web of Science ID A1987K544600004

    View details for PubMedID 3444341

  • CULTURAL AND BIOLOGICAL EVOLUTIONARY PROCESSES - GENE CULTURE DISEQUILIBRIUM PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES Feldman, M. W., CAVALLISFORZA, L. L. 1984; 81 (5): 1604-1607

    Abstract

    The dynamics of the interaction between genetic and cultural transmission are studied by using a simple two-phenotype diallelic haploid genetic system. The value of an individual's phenotype is determined by cultural transmission from its parent or by a randomly chosen member of the parental population. In the absence of phenotypic selection, polymorphic equilibria of the gene and trait frequencies are obtained. The correlation between genotype and phenotype within or between populations depends on a quantity formally similar to linkage disequilibrium and is determined by a relationship among transmission coefficients analogous to a coefficient of epistasis. With natural selection on the phenotype and no mutation, only degenerate transmission rules allow polymorphic equilibria to be attained, and, in general, the genotype allowing the strongest transmission of the favored phenotype is successful.

    View details for Web of Science ID A1984SJ69300069

    View details for PubMedID 6584896

  • PARADOX OF THE EVOLUTION OF COMMUNICATION AND OF SOCIAL INTERACTIVITY PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES CAVALLISFORZA, L. L., Feldman, M. W. 1983; 80 (7): 2017-2021

    Abstract

    Communication between individuals of a species is likely to increase the capacity to acquire skills useful for survival and propagation and thus may confer important selective advantages. Since interaction occurs between two or more individuals, the selective process is frequency dependent, and the analysis shows that communication cannot initially increase at a reasonable rate when it is limited to random unrelated individuals, so that it is likely to abort for stochastic reasons. However, this bottleneck is removed if the communication process takes place in the nuclear family or among close relatives or if aggregation of communicators occurs because of assortative mating or meeting. Use of the individual conditional fitnesses we have introduced earlier permits an exact analysis. We show that, in general, the initial rate of increase can be geometric if and only if, in the class of selective models considered, the conditional probability of a communicator interacting with another contains a positive constant term. In our discussion of communication, cost factors for the act of communication have been omitted. However, the model has been generalized to include cooperativeness, and also altruism, or competition, by introducing costs. There is a close relationship among these situations, and the same considerations about the initial bottleneck and its resolution also extend to them. The models given here are for haploids but they extend to diploids and the conclusions are similar.

    View details for Web of Science ID A1983QJ91900050

    View details for PubMedID 6572958

  • CULTURAL VERSUS GENETIC ADAPTATION PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES CAVALLISFORZA, L. L., Feldman, M. W. 1983; 80 (16): 4993-4996

    Abstract

    We analyze the problem of the competition between genetic and cultural adaptation, testing various types of cultural transmission models versus a genetic (haploid) transmission model. With a vertical (parent-to-child) plus an infectious (oblique) cultural transmission, genetic adaptation always prevails, although its relative increase may be slow and polymorphism may persist for some time. Only under very special conditions of cultural transmission may a permanent polymorphism in which the two types of adaptation are represented be reached. There may, however, be an overall evolutionary advantage to a flexible mechanism of cultural transmission that allows adaptation to new situations for which no genetic mutants are available.

    View details for Web of Science ID A1983RD40300026

    View details for PubMedID 6576371

  • ON SOME MODELS OF FERTILITY SELECTION GENETICS Feldman, M. W., Christiansen, F. B., Liberman, U. 1983; 105 (4): 1003-1010

    Abstract

    Additive, multiplicative and symmetric models of fertility controlled by one diallelic gene are studied. For the completely symmetric fertility system a complete equilibrium and local stability analysis is possible. Contrary to previous conjectures, asymmetric equilibria can be stable. Conditions are derived under which a multiplicative model can be regarded as equivalent to a symmetric fertility system.

    View details for Web of Science ID A1983RR69400015

    View details for PubMedID 17246176

  • A THEORETICAL AND NUMERICAL ASSESSMENT OF GENETIC-VARIABILITY GENETICS Karlin, S., Feldman, M. W. 1981; 97 (2): 475-493

    Abstract

    The equilibrium behavior of one-locus viability selection models is studied numerically. The selection schemes include randomly chosen viabilities, viabilities chosen to measure a hypothetical distance between the alleles making up the genotype and viabilities that obey various allelic dominance relations. From 3 to 8 alleles are considered. Among the key conclusions are (1) equilibria that are most polymorphic do not usually have the highest mean fitness, (2) the more structure there is in the choice of the viability model, the greater is the level of polymorphism at equilibrium, and (3) for the numbers of alleles chosen here, the equilibrium reached by iteration from the centroid of the allele frequency simplex is the best predictor of the equilibrium attainable from randomly chosen starting vectors. Preliminary evidence shows that this is not the case for 16 alleles.

    View details for Web of Science ID A1981MA93500015

    View details for PubMedID 17249079

  • ASSORTATIVE MATING, SELECTION AND MUTATION MODELS FOR CONTINUOUS VARIATION - REPLY THEORETICAL POPULATION BIOLOGY Feldman, M. W., CAVALLISFORZA, L. L. 1981; 19 (3): 370-377
  • Cultural transmission and evolution: a quantitative approach. Monographs in population biology Cavalli-Sforza, L. L., Feldman, M. W. 1981; 16: 1-388

    View details for PubMedID 7300842

  • DENSITY-DEPENDENT FERTILITY SELECTION IN EXPERIMENTAL POPULATIONS OF DROSOPHILA-MELANOGASTER GENETICS Clark, A. G., Feldman, M. W. 1981; 98 (4): 849-869

    Abstract

    The effects of larval density on components of fertility fitness were investigated with two mutant lines of Drosophila melanogaster. The differences in adult body weight, wing length, larval survivorship and development time verified that flies reared at high density were resource limited. Experimental results indicate that: (1) relative fecundities of both sexes show density-dependent effects, (2) there is a strong density effect on male and female mating success, and (3) in general, there is a reduction in fecundity differences between genotypes at high density. These results imply that it may be important to consider fertility in models of density-dependent natural selection.

    View details for Web of Science ID A1981MX82400012

    View details for PubMedID 17249109

  • FURTHER REMARKS ON DARWINIAN SELECTION AND ALTRUISM THEORETICAL POPULATION BIOLOGY Feldman, M. W., CAVALLISFORZA, L. L. 1981; 19 (2): 251-260
  • EVOLUTION OF RECOMBINATION IN A CONSTANT ENVIRONMENT PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES Feldman, M. W., Christiansen, F. B., Brooks, L. D. 1980; 77 (8): 4838-4841

    Abstract

    The theory of evolution at a selectively neutral locus that controls the recombination between two major loci that are under selection is studied. If the major loci are at a stable equilibrium in linkage disequilibrium under selection and recombination, then a mutation at the modifier locus will increase in frequency when rare if and only if it decreases the recombination fraction. If the major loci are in disequilibrium at a balance between selection against deleterious alleles and mutation towards them, then two new phenomena are observed. First, a recombination increasing mutation will succeed if the disequilibrium is negative and the modifier is sufficiently tightly linked to the major loci. Second, depending on the strength of selection, even if the disequilibrium is negative, recombination reduction may occur for looser linkage between the major and modifier loci.

    View details for Web of Science ID A1980KG46700092

    View details for PubMedID 16592864

  • EXPERIMENTAL AND THEORETICAL-ANALYSIS OF THE SEX-RATIO POLYMORPHISM IN DROSOPHILA-PSEUDOOBSCURA GENETICS Curtsinger, J. W., Feldman, M. W. 1980; 94 (2): 445-466

    Abstract

    The Sex-ratio chromosome (SR) is a widespread, multiply inverted rearrangement of the X chromosome present in several species of Drosophila. Male carriers transmit mostly X-bearing sperm. In the absence of strong counteracting selection, SR is expected to increase rapidly to fixation, causing extinction. The present study incorporates a selection-components analysis of SR in laboratory populations, using the closely linked Esterase-5 locus as a marker. Estimated fitnesses show directional viability selection against SR in both males and females, heterosis for fertility and no significant effects on virility, the male adult component of fitness. Estimated fitnesses satisfy conditions for protected polymorphism and accurately predict gene-frequency trajectories in experimental populations. A model of SR gene-frequency evolution is developed, which incorporates sex-linkage, meiotic drive, viability, fertility and virility selecton. We show that conditions for protected polymorphisms are not unduly restrictive and that differential fitness among males is not sufficient for protected polymorphism, irrespective of the degree of meiotic drive.

    View details for Web of Science ID A1980JX23500012

    View details for PubMedID 17249004

  • ASPECTS OF VARIANCE AND COVARIANCE ANALYSIS WITH CULTURAL INHERITANCE THEORETICAL POPULATION BIOLOGY Feldman, M. W., CAVALLISFORZA, L. L. 1979; 15 (3): 276-307

    View details for Web of Science ID A1979HN07600001

    View details for PubMedID 515973

  • On hereditary transmission in diseases of complex etiology. Progress in clinical and biological research Feldman, M. W., Cavalli-Sforza, L. L. 1979; 32: 203-227

    View details for PubMedID 523470

  • EVOLUTION OF CONTINUOUS VARIATION .3. JOINT TRANSMISSION OF GENOTYPE, PHENOTYPE AND ENVIRONMENT GENETICS CAVALLISFORZA, L. L., Feldman, M. W. 1978; 90 (2): 391-425

    Abstract

    Evolutionary models of continuous traits are developed. The models are based on the ideas that: (1) the phenotype is the result of the interaction between genotype and environment; (2) the phenotype is the object of natural selection; (3) not only the genotype but also environmental variables and even phenotypes can be directly transmitted. The phenotype of an offspring at birth is a linear combination of its genotypic value, the phenotypic values of its parents, and their environmental values, all measured on the phenotypic scale. The genetic effects are additive polygenic, and a mutation contribution to the within family variance is admitted.-The values of the offspring phenotype and environment before selection are each linear combinations of these values at birth, the coefficients defining what we call "development." Selection is mostly stabilizing of the Gaussian type, but directional selection is introduced using a Gaussian fitness function with a large variance and a mean far from the current population.-Assortative mating for both phenotype and environment are considered. The analysis in all cases is made by iteration of the means, variances and covariances of the trivariate random variable (genotype, phenotype, environment) whose changes over time completely specify the evolution. In most cases numerical methods are used. The problems of estimating the relative roles of each of the variates in the parents in determining the variates in the offspring are discussed. The major results concern the relative magnitudes of the variances and correlations of the three variates, genotype, phenotype and environment, in a variety of selective, developmental and assorting situations with complex transmission in which G-(genetic), F-(phenotypic), E-(environment) inheritance mechanisms operate jointly. The transmission rules and development patterns (i.e., interactions between phenotype and environment during development) are of major importance in determining qualitative features of the equilibrium distribution.

    View details for Web of Science ID A1978FV72000013

    View details for PubMedID 17248869

  • SIMULTANEOUS STABILITY OF D EQUAL-TO 0 AND D NOT-EQUAL-TO 0 FOR MULTIPLICATIVE VIABILITIES AT 2 LOCI GENETICS Karlin, S., Feldman, M. W. 1978; 90 (4): 813-825

    Abstract

    The two-locus, two-allele multiplicative viability model is investigated. It is shown that the well-known region of recombination values for which D = 0 is locally stable does not preclude the local stability of an equilibrium with D not equal 0. This is shown numerically and is true for every case investigated in which both loci are overdominant and the viabilities not symmetric.

    View details for Web of Science ID A1978GB78600012

    View details for PubMedID 17248876

  • TOWARDS A THEORY OF CULTURAL EVOLUTION INTERDISCIPLINARY SCIENCE REVIEWS CAVALLISFORZA, L. L., Feldman, M. W. 1978; 3 (2): 99-107
  • DARWINIAN SELECTION AND ALTRUISM THEORETICAL POPULATION BIOLOGY CAVALLISFORZA, L. L., Feldman, M. W. 1978; 14 (2): 268-280

    View details for Web of Science ID A1978GA18900007

    View details for PubMedID 746492

  • EVOLUTION OF CONTINUOUS VARIATION .2. COMPLEX TRANSMISSION AND ASSORTATIVE MATING THEORETICAL POPULATION BIOLOGY Feldman, M. W., CAVALLISFORZA, L. L. 1977; 11 (2): 161-181
  • CULTURAL AND BIOLOGICAL EVOLUTIONARY PROCESSES, SELECTION FOR A TRAIT UNDER COMPLEX TRANSMISSION THEORETICAL POPULATION BIOLOGY Feldman, M. W., CAVALLISFORZA, L. L. 1976; 9 (2): 238-259

    View details for Web of Science ID A1976BU02400008

    View details for PubMedID 1273802

  • EVOLUTION OF CONTINUOUS VARIATION - DIRECT APPROACH THROUGH JOINT DISTRIBUTION OF GENOTYPES AND PHENOTYPES .1. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA CAVALLISFORZA, L. L., Feldman, M. W. 1976; 73 (5): 1689-1692

    Abstract

    The evolutionary dynamics of the joint distribution of genotypes and phenotypes is studied. The model, originally devised to study the joint effects of Mendelian and other types of transmissions, provides results of interest also to the theory of direct Mendelian transmission with natural selection. Assuming bivariate normal distributions, it is shown that in the latter case genotypic and phenotypic means and variances, and genotype-phenotype correlation can be expressed recursively as functions of the parameters for the selection, environmental, and mutation variance. Equilibria and rates of approach for these moments are calculated. It is also proved that in the presence of selection the heritability,defined as the ratio of expected genotypic to expected phenotypic variance after selection, is greater than that before selection by a predictable amount and that it can be greater than unity.

    View details for Web of Science ID A1976BS77400071

    View details for PubMedID 1064041

  • SPECIES PACKING AND PREDATION PRESSURE ECOLOGY Roughgarden, J., Feldman, M. 1975; 56 (2): 489-492
  • HERITABILITY HANG-UP SCIENCE Feldman, M. W., Lewontin, R. C. 1975; 190 (4220): 1163-1168

    View details for Web of Science ID A1975AY85500008

    View details for PubMedID 1198102

  • MODELS FOR CULTURAL INHERITANCE - GENERAL LINEAR-MODEL ANNALS OF HUMAN BIOLOGY Feldman, M. W., CAVALLISFORZA, L. L. 1975; 2 (3): 215-226

    Abstract

    A theory of cultural evolution is proposed based on a general linear mode of cultural transmission. The trait of an individual is assumed to depend on the values of the same trait in other individuals of the same, the previous or earlier generation. The transmission matrix W has as its elements the proportional contributions of each individual (i) of one generation to each individual (j) of another. In addition, there is random variation (copy error or innovation) for each individual. Means and variances of a group of N individuals change with time and will stabilize asymptotically if the matrix W is irreducible and aperiodic. The rate of convergence is geometric and is governed by the largest non-unit eigenvalue of W. Groups fragment and evolve independently if W is reducible. The means of independent groups vary at random at a predicted rate, a phenomenon termed "random cultural drift". Variances within a group tend to be small, assuming cultural homogeneity. Transmission matrices of the teacher/leader type, and of parental type have been specifically considered, as well as social hierarchies. Various limitations, extensions, and some chances of application are discussed.

    View details for Web of Science ID A1975AF95300001

    View details for PubMedID 16431675

  • POPULATIONS STATIONARY DISTRIBUTION AND CHANCE OF EXTINCTION IN A STOCHASTIC ENVIRONMENT WITH REMARKS ON THEORY OF SPECIES PACKING THEORETICAL POPULATION BIOLOGY Feldman, M. W., Roughgarden, J. 1975; 7 (2): 197-207

    View details for Web of Science ID A1975W295600005

    View details for PubMedID 1145503

  • SELECTION IN COMPLEX GENETIC SYSTEMS .3. EFFECT OF ALLELE MULTIPLICITY WITH 2 LOCI GENETICS Feldman, M. W., Lewontin, R. C., Franklin, I. R., Christiansen, F. B. 1975; 79 (2): 333-347

    Abstract

    A two-locus model with three alleles at one locus and two at the other is studied. The viability system is such that all double heterozygotes have fitness unity, all single heterozygotes have fitness w smaller than 1 and all double homozygotes have fitness w-2. The following are the major findings: 1. There are more stable equilibria for tight linkage than in the corresponding three-locus model, even though the number of chromosomes is lower. 2. The equilibria stable for tight linkage do not belong to a unique high complementarity class, as is the case for two alleles at each locus. Instead the strength of selection determines the structure of the equilibrium. 3. The increase in number of alleles seems to reduce the possible extent of association between the loci. 4. The measure of this association is not well defined, although we have suggested a statistically standard way of getting over this. 5. A mutation introduced while a population is in linkage disequilibrium may, per medium only of the change in number of alleles, destroy the linkage disequilibrium.

    View details for Web of Science ID A1975AB22300013

    View details for PubMedID 1132683

  • Cultural versus biological inheritance: phenotypic transmission from parents to children. (A theory of the effect of parental phenotypes on children's phenotypes). American journal of human genetics Cavalli-Sforza, L. L., Feldman, M. W. 1973; 25 (6): 618-637

    View details for PubMedID 4797967

  • Models for cultural inheritance. I. Group mean and within group variation. Theoretical population biology Cavalli-Sforza, L., Feldman, M. W. 1973; 4 (1): 42-55

    View details for PubMedID 4726009

  • SELECTION FOR LINKAGE MODIFICATION .2. RECOMBINATION BALANCE FOR NEUTRAL MODIFIERS GENETICS Feldman, M. W., Balkau, B. 1973; 74 (4): 713-726

    Abstract

    A stable polymorphic equilibrium may be established at a selectively-neutral gene locus which controls the extent of recombination between two other selected loci. The condition for the existence of the stable polymorphism is analogous to heterozygous advantage. The heterozygote at the modifying locus should produce a recombination fraction allowing the greatest linkage disequilibrium. In the models treated this has the effect of producing the highest mean fitness. The relationship of these findings to general problems of coadaptation is discussed.

    View details for Web of Science ID A1973R136700016

    View details for PubMedID 17248638

  • SELECTION FOR MIGRATION MODIFICATION GENETICS Balkau, B. J., Feldman, M. W. 1973; 74 (1): 171-174

    Abstract

    Simple models for the genetic control of the tendency to migrate are considered. It is shown that migration from a more favorable regime to a less favorable regime is selected against. The ramifications for general modifier theory are discussed.

    View details for Web of Science ID A1973Q085100012

    View details for PubMedID 17248608

Conference Proceedings


  • ON THE COMPLEXITY OF CULTURAL TRANSMISSION AND EVOLUTION Feldman, M. W., CAVALLISFORZA, L. L., Zhivotovsky, L. A. ADDISON-WESLEY PUBL CO. 1994: 47-64

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