The Natural History of Class I Primate Alcohol Dehydrogenases Includes Gene Duplication, Gene Loss, and Gene Conversion

Abstract

BackgroundGene duplication is a source of molecular innovation throughout evolution. However, even with massive amounts of genome sequence data, correlating gene duplication with speciation and other events in natural history can be difficult. This is especially true in its most interesting cases, where rapid and multiple duplications are likely to reflect adaptation to rapidly changing environments and life styles. This may be so for Class I of alcohol dehydrogenases (ADH1s), where multiple duplications occurred in primate lineages in Old and New World monkeys (OWMs and NWMs) and hominoids.Methodology/Principal FindingsTo build a preferred model for the natural history of ADH1s, we determined the sequences of nine new ADH1 genes, finding for the first time multiple paralogs in various prosimians (lemurs, strepsirhines). Database mining then identified novel ADH1 paralogs in both macaque (an OWM) and marmoset (a NWM). These were used with the previously identified human paralogs to resolve controversies relating to dates of duplication and gene conversion in the ADH1 family. Central to these controversies are differences in the topologies of trees generated from exonic (coding) sequences and intronic sequences.Conclusions/SignificanceWe provide evidence that gene conversions are the primary source of difference, using molecular clock dating of duplications and analyses of microinsertions and deletions (micro-indels). The tree topology inferred from intron sequences appear to more correctly represent the natural history of ADH1s, with the ADH1 paralogs in platyrrhines (NWMs) and catarrhines (OWMs and hominoids) having arisen by duplications shortly predating the divergence of OWMs and NWMs. We also conclude that paralogs in lemurs arose independently. Finally, we identify errors in database interpretation as the source of controversies concerning gene conversion. These analyses provide a model for the natural history of ADH1s that posits four ADH1 paralogs in the ancestor of Catarrhine and Platyrrhine primates, followed by the loss of an ADH1 paralog in the human lineage.

OMA standalone: orthology inference among public and custom genomes and transcriptomes

“…These groups are defined for every internal node of the (rooted) species tree; each HOG contains the genes that are inferred to have descended from a common ancestral gene among the species attached to that internal node. Consider, for instance, gene ADH1, which duplicated within the primates (Carrigan et al 2012): At the level of the last primate common ancestor, all genes that have descended from the ancestral ADH1 belong to the same HOG. However, at the level of the common ancestor of all the great apes, because ADH1 had at this point already duplicated into ADH1A, ADH1B, and ADH1C, these ancestral genes define three HOGs.…”

OMA standalone: orthology inference among public and custom genomes and transcriptomes

“…Consider for instance gene ADH1, which duplicated within the primates (Carrigan et al, 2012) : At the level of the last primate common ancestor, all genes that have descended from the ancestral ADH1 belong to the same HOG. However, at the level of the common ancestor of all the great apes, because ADH1 had at this point already duplicated into ADH1a, ADH1b, and ADH1c, these ancestral genes define 3 HOGs.…”

Alcohol-induced dysregulation of stress-related circuitry: The search for novel targets and implications for interventions across the sexes

“…While alcohol use in antiquity often conjures images of Dionysian debauchery on artefactual Greek hydriai, there is evidence to suggest that fermented fruits contributed to shaping human evolution (Carrigan et al, 2012). Paleogenetic evidence regarding the history of alcohol dehydrogenase (ADH) indicates that this enzyme, critical for the metabolism of alcohol, may have first developed in primates before the divergence of old and new world monkeys.…”

“…Paleogenetic evidence regarding the history of alcohol dehydrogenase (ADH) indicates that this enzyme, critical for the metabolism of alcohol, may have first developed in primates before the divergence of old and new world monkeys. The emergence of the ADH genes at this time point is hypothesized to have both dietary and behavioral consequences as fruits that had fallen from trees and initiated the process of fermentation would now be digestible rather than toxic, opening a previously inaccessible food niche (Brenner, 2013, Carrigan, Uryasev, 2012). Further, according to the Drunken Monkey Hypothesis of Dudley (2004), volatilized alcohols from fruit may have acted as olfactory signals for food localization in early primates.…”