Whole-genome analyses point to new candidate genes underlying aestivation in amphibians
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When amphibians invaded the terrestrial realm, they likely needed a strategy such as aestivation to survive water and oxygen stress in the novel environment. In fact, aestivation appears to be an ancestral state in amphibians. We conducted a literature review about the genes previously linked to aestivation and then we searched for additional candidate genes related to the aestivation phenotype by comparing evolutionary rates of 13,578 genes in 31 amphibian species, including 10 aestivating species and 21 non-aestivating species. Based on the assumption that aestivation has two main requirements – a) metabolic regulation needed to control transitions to/from the hypometabolic state, and b) cell preservation strategies needed to sustain biological processes over long-term dormancy – we expected to find distinct relative evolutionary rates (RER) in genes related to those traits. We identified 323 genes with significant RERs; these genes were enriched for some processes overlapping with our predictions and with literature findings, such as shifts between glycolysis and oxidative phosphorylation. Other genes related to protein and membrane trafficking (TRAPP, SNARE, and Arp2/3 complexes) are newly associated with aestivation. RER patterns suggest that aestivation 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 aestivating amphibian lineages, we predict that more in-depth molecular studies of amphibian aestivation 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.
What is already known
Over 300 million years ago, the ancestors of amphibians were the first vertebrates to emerge onto land, and they likely experienced intense physiological stresses. To this day, many amphibians have retained the ability to survive water and heat stress through aestivation, a hypometabolic state during which animals suspend their daily activities. How aestivation is induced and maintained is of medical interest because these animals can live in suspended animation for months or even years at a time, while retaining the ability to awaken without organ atrophy or cancerous tissues. The genetics of aestivation are just beginning to be understood, but much remains to be discovered.
What this study adds
This study uses newly available genomic resources for amphibians and new genome-wide analysis tools to provide novel insight into the genes and processes underlying aestivation. The genome-wide assessment and inclusion of species not previously studied from a genetic perspective provides novel candidate processes involved in aestivation like angiogenesis and protein and membrane trafficking. The diversity of amphibians that aestivate is much greater than in other vertebrate groups and represents a relatively untapped resource that can inspire future innovations in human medicine.
