Genetic evidence of widespread variation in ethanol metabolism among mammals: Revisiting the ‘myth’ of natural intoxication

Abstract

Humans have a long evolutionary relationship with ethanol, pre-dating anthropogenic sources, and possess unusually efficient ethanol metabolism, through a mutation that evolved in our last common ancestor with African great apes. Increased exposure to dietary ethanol through fermenting fruits and nectars is hypothesized to have selected for this in our lineage. Yet, other mammals have frugivorous and nectarivorous diets, raising the possibility of natural ethanol exposure and adaptation in other taxa. We conduct a comparative genetic analysis of alcohol dehydrogenase class IV (ADH IV) across mammals to provide insight into their evolutionary history with ethanol. We find genetic variation and multiple pseudogenization events in ADH IV, indicating the ability to metabolize ethanol is variable. We suggest that ADH enzymes are evolutionarily plastic and show promise for revealing dietary adaptation. We further highlight the derived condition of humans and draw attention to problems with modelling the physiological responses of other mammals on them, a practice that has led to potentially erroneous conclusions about the likelihood of natural intoxication in wild animals. It is a fallacy to assume that other animals share our metabolic adaptations, rather than taking into consideration each species’ unique physiology.