title: Hominids adapted to metabolize ethanol long before human-directed fermentation.
abstract: Paleogenetics is an emerging field that resurrects ancestral proteins from now-extinct organisms to test, in the laboratory, models of protein function based on natural history and Darwinian evolution. Here, we resurrect digestive alcohol dehydrogenases (ADH4) from our primate ancestors to explore the history of primate-ethanol interactions. The evolving catalytic properties of these resurrected enzymes show that our ape ancestors gained a digestive dehydrogenase enzyme capable of metabolizing ethanol near the time that they began using the forest floor, about 10 million y ago. The ADH4 enzyme in our more ancient and arboreal ancestors did not efficiently oxidize ethanol. This change suggests that exposure to dietary sources of ethanol increased in hominids during the early stages of our adaptation to a terrestrial lifestyle. Because fruit collected from the forest floor is expected to contain higher concentrations of fermenting yeast and ethanol than similar fruits hanging on trees, this transition may also be the first time our ancestors were exposed to (and adapted to) substantial amounts of dietary ethanol.
authors.affiliation: Department of Natural Sciences, Santa Fe College, Gainesville, FL 32606; Foundation for Applied Molecular Evolution, Gainesville, FL 32604; and matthew.carrigan@sfcollege.edu.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Carrigan
authors.affiliation: Foundation for Applied Molecular Evolution, Gainesville, FL 32604; and.
authors.forename: Oleg
authors.initials: O
authors.lastname: Uryasev
authors.affiliation: Foundation for Applied Molecular Evolution, Gainesville, FL 32604; and.
authors.forename: Carole B
authors.initials: CB
authors.lastname: Frye
authors.affiliation: Foundation for Applied Molecular Evolution, Gainesville, FL 32604; and.
authors.forename: Blair L
authors.initials: BL
authors.lastname: Eckman
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202.
authors.forename: Candace R
authors.initials: CR
authors.lastname: Myers
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Hurley
authors.affiliation: Foundation for Applied Molecular Evolution, Gainesville, FL 32604; and.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Benner
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000426:Alcohol Dehydrogenase / Q000145:classification / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D004032:Diet; D000431:Ethanol / Q000378:metabolism*; D019143:Evolution, Molecular; D005285:Fermentation / Q000235:genetics; D005638:Fruit / Q000378:metabolism; D014644:Genetic Variation; D015186:Hominidae / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D011323:Primates / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D000431:Ethanol; D000426:Alcohol Dehydrogenase; C105552:alcohol dehydrogenase IV
keywords: alcohol dehydrogenase; ethanol; evolution; experimental paleogenetics; primates