Nathan Clark

Nathan Clark, Ph.D.
Assistant Professor

Ph.D. in Genome Sciences at University of Washington, Seattle

3501 Fifth Avenue
3080 Biomedical Science Tower 3
Pittsburgh, PA 15260

Phone: (412) 855-4562
Website: /faculty/clark/

Research Summary

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 seek to identify coevolutionary signatures between genes that function in a common pathway or complex. We then exploit these signatures to infer new genetic interactions and reveal deeper relationships between entire genetic pathways. To date we have performed genome-wide coevolution studies in yeasts and in Drosophila species, in both cases providing novel functional insight. We will now compare and contrast these results with the coevolution found within mammalian species. (2) 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 for 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.

Recent Publications

Ziegler AB, Augustin H, Clark NL, Berthelot-Grosjean M, Simonnet MM, Steinert JR, Geillon F, Manière G, Featherstone DE, Grosjean Y (2016) The Amino Acid Transporter JhI-21 Coevolves with Glutamate Receptors, Impacts NMJ Physiology, and Influences Locomotor Activity in Drosophila Larvae Sci Rep 6:19692.

Böhm S, Szakal B, Herken BW, Sullivan MR, Mihalevic MJ, Kabbinavar FF, Branzei D, Clark NL, Bernstein KA (2016) The Budding Yeast Ubiquitin Protease Ubp7 is a Novel Component Involved in S-phase Progression J Biol Chem [Epub ahead of print]

Wolfe NW, Clark NL (2015) ERC Analysis: web-based inference of gene function via Evolutionary Rate Covariation Bioinformatics 31(23):3835-7.


Project title Proj Start Date Proj End Date Funding Source
Center for Causal Modeling and Discovery of Biomedical Knowledge from Big Data 9/29/2014 8/31/2018 NHGRI-U54
CAREER: Regulation of Cargo Selection and Ubiquitination by Protein Trafficking Adaptors 1/1/2016 12/31/2020 NSF