Genetic evidence of widespread variation in ethanol metabolism among mammals

This is an excellent topic for gene-environment interactions. The environmental signal is “alcohol” (ethanol; EtOH) and the response is enjoyment of drinking vs averson to drinking EtOH shows great variability among individuals in the same species, as well as differences between species; these differences in response to this signal reflect alterations of genes in the genome. Figure 1 [see attached article] shows protein variations in aldehyde dehydrogenase-7 (ADH7) combined with evolutionary relationships and diets of ~90 species included in this publication’s analysis. It has been hypothesised that our enjoyment of drinking EtOH can be traced evolutionarily to fruit-eating ancestors that were exposed to naturally

occurring alcohol in ripening fruits. In fact, chimpanzees and other primates are exceptionally sensitive to odors of

aliphatic alcohols including EtOH, and at some prefer drinking EtOH-containing solutions over water.

Humans, chimpanzees, bonobos and gorillas have the same mutation in the ADH7 gene (Ala294Val in the protein), which results in being able to metabolize EtOH ~40 times more rapidly. The evolutionary time of appearance of this mutation (~10 million years ago) coincides with increased terrestriality (i.e. living on the ground rather than in trees or water) in our lineage — which likely led to more frequent exposure to fermenting fruit on the forest floor. Other animals that seek out EtOH for consumption include aye-ayes (long-fingered lemur living in Madagascar), tree shrews, elk and other ungulates (hoofed mammals), many bird species (e.g. robins and blue jays will soon be robbing us of most of our blueberries), and fruit-eating bats — and there are many anecdotal stories of intoxication in all these species…!!

Authors [see attached article] conducted a comparative genetic analysis of the ADH7 gene — across ~90 mammalian species to provide insight into their evolutionary history with EtOH. Authors demonstrate genetic variation, including several different events that lead to a pseudogene [i.e. one means of inactivating the enzyme is to make the gene unable to translate a functional protein; another means is to translate a protein that is (still) unable to metabolize EtOH] in ADH7, indicating the ability to metabolize EtOH varies with the species. Table 1 [of attached article] provides a list of the genetic ways that lead to an inability to break down EtOH in various mammalian species.

Authors suggest that ADH enzymes are evolutionarily plastic, revealing dietary adaptation of each individual species. It is a fallacy to assume that other animals share our metabolic adaptations, rather than taking into consideration each species’ unique physiology. A topic not covered in this overview is that different inbred strains of the same species (e.g. mice, rats) — as well as ethnic differences among humans — exhibit EtOH preference vs EtOH aversion. 😊 ☹


Biol Lett Apr 2020; 16: 20200070

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