David Kingsley

Administrative Appointments

• Director, NIH Center of Excellence in Genomic Science at Stanford: The Genomic Basis of Vertebrate Diversity (2007 - 2012)

Honors and Awards

• Member, National Academy of Sciences (2011)
• Conklin Medal, Society for Developmental Biology (2009)
• Fellow, American Academy of Arts and Sciences (2005)
• Researcher, Howard Hughes Medical Institute (1997 to present)
• Scholar in Biomedical Research, Lucille P. Markey Foundation (1989 to 1996)

Professional Education

Postdoctoral Advisees

Terence Capellini

Graduate & Fellowship Program Affiliations

• Developmental Biology
• Neurosciences

Community and International Work

• Stickleback Genome Project and Summer Training Course, Stanford 

Internet Links

• http://kingsley.stanford.edu
• Kingsley Lab Homepage

Current Research Interests

Naturally occurring species show spectacular differences in morphology, physiology, lifestyle, and behavior. They also differ in disease susceptibility and life span. Although the genomes of many organisms have now been completely sequenced, we still know relatively little about the specific DNA sequence changes that underlie interesting species-specific traits. My laboratory is using a combination of genetic and genomic approaches to identify the detailed molecular mechanisms that control evolutionary change in vertebrates, with a focus on five fundamental questions:

1. Are new evolutionary traits controlled by countless genetic differences of small effect, or by a few genetic changes with large effects?

2. What specific genes have changed to produce interesting evolutionary differences seen in nature?

3. What kinds of mutations have occurred in these genes (e.g., dominant or recessive, coding or regulatory, preexisting or de novo)?

4. How predictable is evolution? If you know how evolution has occurred in one population, is it possible to predict the genes and mutations that also underlie the same trait in different populations?

5. How has evolution produced the unique characteristics of humans?

We study these questions using a variety of methods in  mice, sticklebacks, and people.

Mice are often the best system available for asking detailed mechanistic questions in mammals, or testing the phenotypic effects of particular sequence changes seen in other species. We have used classical genetics in mice to identify fundamental pathways that control formation and patterning of cartilage, bone, and joints. We also make extensive use of mice identifying the regulatory mechanisms that lay out expression of key developmental control genes, with the ultimate aim of identifying how vertebrate morphology itself is encoded in the genome.

Sticklebacks offer an unusually powerful system for studying the molecular basis of evolutionary change in naturally occurring species.  Our lab has pioneered the development of a large number of new  genetic and genomic resources for the fish, and has worked with Hudson Alpha Institute and the Broad Institute to develop a mapped, whole genome sequence assembly for sticklebacks.  Using these new tools, we have now successfully identified both the molecular mechanisms that control repeated evolution of armor plate patterning, pelvic reduction, and skin color changes in nature. Our studies show that big evolutionary changes can be controlled by single chromosome regions.   The big changes are controlled by alterations in major developmental control genes (key signaling molecules and transcription factors).  Although null mutations in these genes are typically deleterious or lethal, sticklebacks have made regulatory alterations in these genes that produce large morphological effects in particular tissues, while preserving overall viability.  Interestingly, the same genes are used repeatedly when similar phenotypes evolve in different populations, revealing a surprising commonality to the molecular mechanisms that control rapid evolutionary change in diverse organisms.

Although many of our studies have begun in mice or sticklebacks,  the genes and mechanisms that we  have   also turn out to control major differences in human morphology, human arthritis and cancer incidence, and differences in skin color in billions of people around the world.  Building on this work, we  have now  begun a variety of  projects to identify other mechanisms responsible for interesting evolutionary traits in humans.  Although we are still far from knowing the detailed molecular basis of most human traits, we are optimistic that many aspects of this  problem can now be studied both computationally and experimentally, and will provide new insights into how humans have evolved and adapted to many environments around the world.

Publications

• The genomic basis of adaptive evolution in threespine sticklebacks. Jones FC, Grabherr MG, Chan YF, Russell P, Mauceli E, Johnson J, Swofford R, Pirun M, Zody MC, White S, Birney E, Searle S, Schmutz J, Grimwood J, Dickson MC, Myers RM, Miller CT, Summers BR, Knecht AK, Brady SD, Zhang H, Pollen AA, Howes T, Amemiya C, Baldwin J, Bloom T, Jaffe DB, Nicol R, Wilkinson J, Lander ES, Di Palma F, Lindblad-Toh K, Kingsley DM. Nature. 2012; 484 (7392): 55-61
• Human-specific loss of regulatory DNA and the evolution of human-specific traits. McLean CY, Reno PL, Pollen AA, Bassan AI, Capellini TD, Guenther C, Indjeian VB, Lim X, Menke DB, Schaar BT, Wenger AM, Bejerano G, Kingsley DM. Nature. 2011; 471 (7337): 216-9
• Adaptive evolution of pelvic reduction in sticklebacks by recurrent deletion of a Pitx1 enhancer. Chan YF, Marks ME, Jones FC, Villarreal G, Shapiro MD, Brady SD, Southwick AM, Absher DM, Grimwood J, Schmutz J, Myers RM, Petrov D, Jónsson B, Schluter D, Bell MA, Kingsley DM. Science. 2010; 327 (5963): 302-5
• Shaping skeletal growth by modular regulatory elements in the Bmp5 gene. Guenther C, Pantalena-Filho L, Kingsley DM. PLoS Genet. 2008; 4 (12): e1000308
• Role of the mouse ank gene in control of tissue calcification and arthritis. Ho AM, Johnson MD, Kingsley DM. Science. 2000; 289 (5477): 265-70