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Evolutionary Adaptation to Extreme Environments / Assignment of Function to Genetic Elements

My group is focused on the process of Adaptive Evolution, during which species adopt novel traits to overcome challenges. We study the evolutionary patterns of genomic elements to determine the genetic changes underlying adaptation and to discover previously unknown genetic networks. These discoveries have already led to advances in human health, species conservation, and basic molecular biology. To meet these goals we have developed a suite of computational and experimental approaches employing comparative genomics and proteomics. Ultimately, our research program develops an evolutionary model in which genomic elements are shaped by their co-evolution with other elements and their environment.

Research

Convergent Evolution – Co-evolution between genes and their environment

Convergent evolution describes the independent acquisition (or loss) of a trait in different evolutionary lineages, often in response to the same adaptive pressure. Convergent evolution has been documented at the level of morphology and physiology in many examples including hind limb reduction in swimming mammals and oxygen affinity in species at altitude. The powerful consequence of convergent evolution is that multiple independent realizations of the phenotype provide statistical leverage to identify shared genetic elements underlying that phenotype, even amid the substantial noise in whole-genome scans.

Our work in convergent evolution addresses two driving needs: 1) To identify adaptive changes that evolve in response to environmental challenges, and 2) to assign high-level biological functions to genomic elements. To achieve these goals we have created the RERconverge R package [https://github.com/nclark-lab/RERconverge] to computationally scan for genes and regulatory sequences underlying convergent phenotypes. To date we’ve applied this and other genomic/proteomic approaches to the evolution of aquatic adaptation, subterranean mammals, and long lifespan.

Aquatic Adaptation and Diving

Mammalian lineages have undergone the transition to an aquatic lifestyle many times. We have aimed multiple computational and experimental efforts to understand which adaptations accompany this transition. Adaptations include changes to the lungs, skin, and mechanisms to combat oxidative stress, among others. Many of these adaptations are related to the ability to make repeated and prolonged dives and to abrogate the damage done by diving cycles.

Subterranean Mammals and Regressive Evolution of the Eye.

The lab also studies the evolutionary changes accompanying transition to a subterranean environment. Many of these are regressive changes related to degeneration of the eye. Because genetic regions involved in eye development and function are degrading in these blind species, their contrast with sighted species is a powerful method to identify new genes and regulatory regions important for ocular function. We are experimentally characterizing these new regions in animal models and sequencing them in patients with congenital eye disease for use as new diagnostic regions.

Evolutionary Rate Covariation (ERC) – Co-evolution between genes

We have advanced a computational method to study sequence-based signatures of co-evolution between genes, termed Evolutionary Rate Covariation (ERC). Generally, genes participating in the same biological function have higher ERC correlations than genes in disparate functions. As such, ERC has been used to identify new genes participating in specific pathways of interest for labs around the world. We also offer ERC results through a public web server (http://csb.pitt.edu/erc_analysis).

Lab Members

Principal Investigator

Nathan Clark, Ph.D.

Associate Professor

Lab

Contact

Address

Department of Human Genetics
University of Utah
Human Genetics
15 N 2030 E RM 6120
Salt Lake City, Utah 84112-5330

Phone

422-855-4562

Fax

801-581-7796

Publications

Google Scholar Link:

https://scholar.google.com/citations?user=qp_jN7wAAAAJ&hl=en

Selected Publications:

Wynn K. Meyer, Jerrica Jamison, Rebecca Richter, Stacy E. Woods, Charles Kronk, Raghavendran Partha, Amanda Kowalczyk, Maria Chikina, Robert K. Bonde, Joseph Gaspard, Janet M. Lanyon, Clement E. Furlong, and Nathan L. Clark. Ancient convergent losses of PON1 yield deleterious consequences for modern marine mammals. Science. 2018; 361(6402): 591-594. doi:10.1126/science.aap7714

Partha R, Chauhan BK, Worman-Ferreria Z, Robinson JD, Lathrop K, Nischal KK, Chikina M*, Clark NL*. Subterranean mammals show convergent regression in ocular genes and enhancers, along with adaptation to tunneling. eLife. 2017; 6: e25884.

Meslin C, Cherwin TS, Plakke MS, Small BS, Goetz BJ, Morehouse NI, Clark NL. Structural complexity and molecular heterogeneity of a butterfly ejaculate reflect a complex history of selection. Proceedings of the National Academy of Sciences, USA. 2017; 114(27): E5406–E5413. PMC5502654. Featured in The Atlantic.

Chikina M, Robinson JD, Clark NL. Hundreds of genes experienced convergent shifts in selective pressure in marine mammals. Molecular Biology and Evolution. 2016. 33(9): 2182-2192.

Priedigkeit NM, Wolfe NW, Clark NL. Evolutionary signatures amongst disease genes permit novel methods for gene prioritization and construction of informative gene networks. PLOS Genetics. 2015; 11(2): e1004967. PMC4334549