Subterranean Fishes of the World

3086

2015

AIM 2015

Adaptation to new environment necessitates changes in morphology, behavior, and physiology. While we now have a better understanding of morphological and behavioral evolution, how physiology evolves is still mysterious. Here we use independently derived populations of Mexican cavefish, Astyanax mexicanus, to elucidate the genetic basis of population level metabolic changes associated with the colonization of nutrient poor environment. Many cavefish populations rely on sporadic flooding for nourishment as caves lack primary producers. Thus to survive, cavefish evolved a range of adaptations including starvation resistance and binge eating when food becomes available. We found that the use of these adaptive strategies differs among independently derived populations. While all cavefish populations tested lose weight more slowly than their surface counterparts, only a subset of cavefish populations exhibit the hyperphagia phenotype. A candidate gene approach identified coding mutation in conserved residues of the melanocortin 4 receptor (MC4R) gene, contributing to the insatiable appetite found in some populations of cavefish. Intriguingly, one of the mutated residues has been shown to be linked to obesity in humans. We demonstrate that the allele results in both reduced maximal response and reduced basal activity in vitro. We further validate in vivo that the mutated allele contributes to elevated appetite, growth and starvation resistance. The allele appears to be fixed in cave populations in which the overeating phenotype is present. The presence of the same allele in multiple caves appears to be due to selection from standing genetic variation present in surface populations.

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