Diet and the evolution of ADH7 across seven orders of mammals

Dietary variation within and across species drives the eco-evolutionary
responsiveness of genes necessary to metabolize nutrients and other
components. Recent evidence from humans and other mammals suggests that
sugar-rich diets of floral nectar and ripe fruit have favored mutations
in, and functional preservation of, the ADH7 gene, which encodes the ADH
class 4 enzyme responsible for metabolizing ethanol. Here we interrogate a
large, comparative dataset of ADH7 gene sequence variation, including the
amino acid residue located at key site 294 that regulates the affinity of
ADH7 for ethanol. Our analyses span 171 mammal species, including 59 newly
sequenced. We report extensive variation, especially among frugivorous and
nectarivorous bats, with potential for functional impact, and widespread
variation in the retention and probable pseudogenization of ADH7. However,
we find little statistical evidence of a broad impact of diet on putative
ADH7 function or tuning at site 294 across mammals, suggesting that the
evolution of ADH7 is shaped by complex factors. Our study reports
extensive new diversity in a gene of longstanding ecological interest,
offers new sources of variation to be explored in functional assays in
future studies, and advances our understanding of the processes of
molecular evolution.