Assessing Genetic Adaptations for Ethanol Metabolism using Comparative Genetics

Date
2022-04
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Abstract

Ethanol naturally occurs in fermenting fruits and nectars consumed by mammals. To avoid harmful side effects of ethanol consumption, natural selection might have favoured the persistence and spread of genetic variants that improve ethanol metabolism in frugivorous and nectarivorous mammals. Variation in humans and other primates has fueled debate over adaptive hypotheses, which will be informed by a better understanding of comparative variation across mammals. Ethanol is primarily metabolized via enzymes encoded by ADH and ALDH genes. I studied these genes along with the CAT gene across a range of mammals with diverse diets. I used bioinformatics tools to look for evidence of positive selection in species with high dietary ethanol exposure due to reliance on fruits and/or nectars, relaxed selection in species with low dietary ethanol exposure, and convergent evolution among diverse frugivorous and/or nectarivorous species. Among genes of interest, the ADH7 gene is critical for ethanol metabolism in humans. I additionally investigated amino acid variation at a site (294) within the ADH class IV enzyme (encoded by ADH7) that is important for enzymatic function. I found no evidence of positive selection or of excess non-random convergent substitutions across ADH, ALDH, and CAT genes. However, I did find evidence that several ALDH genes and the CAT gene are under intensified or relaxed selection in lineages with low dietary ethanol exposure. Finally, I found that several leaf-nosed bats, a flying fox, and several opossums vary with the amino acid they possess at site 294. I also identified premature stop codons along ADH7 in two leaf-nosed bats, a rodent, a shrew, two sloths, and two opossums. Intensified selection on the ALDH genes and CAT gene suggest these genes are involved in important bodily processes that have led to their maintenance. Variation at the critical site of ADH7 in bats may indicate increased efficiency for ethanol metabolism in these species. My findings suggest variation in the strength of selection pressures acting on genes underlying ethanol metabolism and potentially adaptive variation in the ADH7 gene. Together these findings extend our understanding of molecular variation in the context of dietary ecology.

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Keywords
Diet, Mammals, Evolution, Primates, Bats, Frugivory, Nectarivory, Ethanol Metabolism, Molecular Adaptation
Citation
Pinto, S. (2022). Assessing genetic adaptations for ethanol metabolism using comparative genetics (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.