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Nathan Clark

Nathan Clark, Ph.D.
Associate 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: Clark Lab

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
Chikina M, Robinson JD, Clark NL (2016) Hundreds of Genes Experienced Convergent Shifts in Selective Pressure in Marine Mammals Mol Biol Evol.. 33(9): 2182–2192

Clancy CJ, Meslin C, Badrane H, Cheng S, Losada LC, Nierman WC, Vergidis P, Clark NL, Nguyen MH (2016) Candida albicans Transcriptional Profiling Within Biliary Fluid From a Patient With Cholangitis, Before and After Antifungal Treatment and Surgical Drainage Open Forum Infect Dis. 3: 3 ofw120

Hancks DC, Hartley MK, Hagan C, Clark NL, Elde NC (2015) Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1 Suggest a Common Mechanism of Pathogen Antagonism and Escape PLoS Genet. 11: 5


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
Functional Annotation of Genomes via Phenotypic Convergence 5/1/2017 4/30/2022 NIH-R01