Whole-Genome Analyses Point to New Candidate Genes Underlying Estivation in Amphibians

AbstractWhen amphibians invaded the terrestrial realm, a strategy such as estivation may have helped them survive water and oxygen stress in the novel environment. In fact, estivation appears to be an ancestral state in amphibians. We conducted a literature review about the genes previously linked to estivation, and then we searched for additional candidate genes related to the estivation phenotype by comparing evolutionary rates of 13,578 genes in 31 amphibian species, including 10 estivating species and 21 nonestivating species. Based on the assumption that estivation has two main requirements-(1) metabolic regulation needed to control transitions to/from dormancy and (2) cell preservation strategies needed to sustain biological processes over long-term dormancy-we expected to find distinct relative evolutionary rates (RERs) in genes related to those traits. We identified 323 genes with accelerated or decelerated RERs; these genes were enriched for some processes overlapping with our predictions and with literature findings, such as different modes of ATP production. Other genes related to protein and membrane trafficking (TRAPP, SNARE, and Arp2/3 complexes) are newly associated with estivation. RER patterns suggest that estivation in amphibians relies on a set of highly conserved core processes and other auxiliary processes that have diversified across the phylogeny. Given the vast number and diversity of estivating amphibian lineages, we predict that more in-depth molecular studies of amphibian estivation will offer novel insight into hypometabolic processes that could inspire medical innovations to prevent organ atrophy, address problems with angiogenesis, and combat processes underlying cancer.