Nathan Clark, Ph.D.

  • Assistant Professor
  • Department of Computational and Systems Biology

Education & Training

  • Ph.D., Genome Sciences, University of Washington, 2007
  • B.S., Chemistry, University of Texas at Austin, 1998

Research Interest Summary

Evolutionary Genomics: We combine computational analysis with evolutionary experiments to determine gene function and to reveal the genetic changes underlying adaptation between species.

Research Categories

Research Interests

Efforts to understand genes and genomes are greatly enhanced by evolutionary analyses. In our group we combine evolutionary inference with direct experiments to determine the relationships between genes and to reveal the genetic changes underlying adaptation between species. Current projects are:

  1. We identify evolutionary signatures between genes that function in a common pathway or complex. We then exploit this signature, termed Evolutionary Rate Covariation (ERC), to infer new genetic interactions and reveal deeper relationships between entire genetic pathways. To date we have performed genome-wide ERC studies in mammals, yeasts, and Drosophila species, in each case providing novel functional insight. Specifically, we have used ERC to infer novel genes in Drosophila mating behavior and in membrane protein trafficking in yeast and mammalian cells.
  2. We study compensatory co-evolution between interacting proteins using both the historical co-evolution between them and laboratory evolution experiments to determine the range of potential compensatory paths. Experimentally, we create and resolve genetic incompatibilities through transgenic experiments in baker’s yeast (Saccharomyces cerevisiae). By mutating a select few amino acids or substituting an entire protein complex from one species to that of another, we follow the effects of co-evolved amino acid changes via phenotypic and physical interaction assays.
  3. We study the adaptive evolution of proteins involved in sexual reproduction and how their divergence contributes to reproductive incompatibilities between individuals. We identify historical cases of adaptive evolution in sperm and egg proteins to explore their changing molecular interactions and to determine the driving forces behind their adaptive evolution.

Representative Publications

Clark NL, Swanson WJ. Pervasive adaptive evolution in primate seminal proteins. PLoS Genetics 2005; 1(3): e35. PMC1201370.

Clark NL, Aagaard JE, Swanson WJ. Evolution of reproductive proteins from animals and plants. Reproduction 2006; 131(1): 11-22. PMC16388004.

Clark NL, Findlay GD, Yi X, MacCoss MJ, Swanson WJ. Duplication and selection on abalone sperm lysin in an allopatric population. Molecular Biology and Evolution. 2007; 24(9): 2081. PMC17630281.

Dean MD, Clark NL, Findlay GD, Karn RC, Yi X, Swanson WJ, MacCoss MJ, Nachman MJ. Proteomics and comparative genomic investigations reveal heterogeneity in evolutionary rate of male reproductive proteins in mice (Mus domesticus). Molecular Biology and Evolution. 2009; 26(8): 1733. PMC2734151.

Clark NL, Gasper J, Sekino M, Springer SA, Aquadro CF, Swanson WJ. Coevolution of interacting fertilization proteins. PLoS Genetics 2009; 5(7): e1000570. PMC2704960.

Clark NL, Aquadro CF. A novel method to detect proteins evolving at correlated rates: Identifying new functional relationships between coevolving proteins. Molecular Biology and Evolution. 2010; 27(5):1152-61. PMC2877527. Featured in Faculty of 1000.

Kelleher ES, Clark NL, Markow TA. Diversity Enhancing Selection Acts on a Female Reproductive Protease Family in Four Sub-Species of Drosophila mojavensis. Genetics. 2011; 187(3): 865-76. PMC3063679.

Clark NL, Alani E, Aquadro CF. Evolutionary rate covariation reveals shared functionality and co-expression of genes. Genome Research. 2012; 22(4): 714-720. PMC3317153.

Clark NL, Alani E, Aquadro CF. Evolutionary rate covariation involving meiotic proteins results from fluctuating evolutionary pressure in yeasts and mammals. Genetics. 2013; 193(2): 529-538. PMC23183665. Selected for Issue Highlight.

Findlay GD, Sitnik JL, Wang W, Aquadro CF, Clark NL, Wolfner MF. Evolutionary Rate Covariation Identifies New Members of a Protein Network Required for Drosophila Female Post-Mating Responses. PLOS Genetics. 2014; 10(1): e1004108. PMC3894160.

Full List of Publications