Evolutionary genetics of an alternative molecular mechanism of hypoxia response in metazoans

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Environments with decreased levels of available oxygen impose highly stressful conditions for animals. Exacerbated by global climate change, hypoxia in ocean waters has been rapidly increasing in frequency and severity, and this has adversely affected populations of marine organisms, including common fishes and crustaceans. In animals, hypoxia results in pronounced cellular physiological responses that are controlled by a suite of master regulatory genes, called the hypoxia-inducible factor (HIF) pathway. The HIF pathway has been widely studied in many groups of animals and was hypothesized to be conserved in all species. Very recent genomic analyses in marine crustaceans, however, revealed that several common and abundant species have lost this set of genes, but are still very tolerant to temporary hypoxic conditions. These species therefore have evolved a different yet still unknown genetic mechanism of dealing with hypoxia. Discovering and characterizing these novel cellular and genetic processes is the main focus of this project and will provide a broader and more complete understanding of how animals adapt to stressful environments. The researchers will engage undergraduate students from first-generation or underrepresented groups in STEM through multiple routes, including encouraging participation in all stages of the project, from data collection to conference presentation and publication, as well as coordinating various research and training workshops in conjunction with the Louis Stokes Alliance for Minority Participation (LSAMP) program at OSU.How we understand the genetic and physiological processes associated with how animals deal with hypoxia have been learned from species with the HIF regulatory machinery. This project will investigate alternative genetic mechanisms of hypoxia response in the intertidal copepod Tigriopus californicus, which is one of the species recently shown to have lost the HIF pathway, but which still exhibit robust tolerance to extreme hypoxic conditions. A major goal of the work is to unmask what transcription factors have evolved to fill the role of HIF-1 in its absence, and what physiological responses are controlled by these new master regulators. The location of open chromatin regions will be identified in copepods under hypoxic stress, which will permit computational prediction of candidate transcription factors. Quantitative and functional genetic experiments will use both natural populations (capturing long term adaptation to environmental hypoxia) and lab populations selected for increased hypoxia tolerance (short term adaptation with strong selection). Among experimental approaches, whole genome sequencing will be used to map loci associated with natural variation in hypoxia response as well as to quantify the trajectory of allele frequencies during laboratory evolution. Finally, recombinant inbred lines will be used to estimate gene co-expression networks and to test correlations of physiological phenotypes with hypoxia-response transcription modules. Findings of this project will likely reveal important functions for previously unknown genes and new ways in which genes and proteins interact to maintain homeostasis during low oxygen stress.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.