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Rapid birth-death evolution and positive selection in detoxification-type glutathione S-transferases in mammals.

ABSTRACT: Glutathione S-Transferases (GSTs) are phase II detoxification enzymes that may have evolved in response to changes of environmental substrates. GST genes formed a multigene family and in mammals, there are six classes known as Alpha, Mu, Omega, Pi, Theta, and Zeta. Recent studies in phase I detoxification system specifically the cytochrome P450s provided a general explanation on why genes from a common origin such as those in a multigene family have both phylogenetically stable and unstable genes. Genes that participate in core functions of organisms such as development and physiology are stable whereas genes that play a role in detoxification are unstable and evolve in a process known as birth-death evolution, which is characterised by frequent gene gains and losses. The generality of the birth-death model at explaining the evolution of detoxification enzymes beyond the phase I enzyme has not been comprehensively explored. This work utilized 383 Gst genes and 300 pseudogenes across 22 mammalian species to study gene gains and losses. GSTs vary greatly in their phylogenetic stability despite their overall sequence similarity. Stable Gst genes from Omega and Zeta classes do not show fluctuation in gene numbers from human to opossum. These genes play a role in biosynthesis related functions. Unstable genes that include Alpha, Mu, Pi and Theta undergo frequent gene gain and loss in a process known as birth-death evolution. Gene members of these four classes are well known for their roles in detoxification. Our positive selection screen identified five positively selected sites in mouse GSTA3. Previous studies showed two of these sites (108H and 208E) were biochemically tested as important residues that conferred catalytic activity against the toxic aflatoxin B1-8,9-epoxide. The functional significance against aflatoxin of the remaining three positively selected sites warrant further investigation.

SUBMITTER: Tan HM

PROVIDER: S-EPMC6306238 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Rapid birth-death evolution and positive selection in detoxification-type glutathione S-transferases in mammals.

Tan Hui Ming HM Low Wai Yee WY

PloS one 20181226 12

Glutathione S-Transferases (GSTs) are phase II detoxification enzymes that may have evolved in response to changes of environmental substrates. GST genes formed a multigene family and in mammals, there are six classes known as Alpha, Mu, Omega, Pi, Theta, and Zeta. Recent studies in phase I detoxification system specifically the cytochrome P450s provided a general explanation on why genes from a common origin such as those in a multigene family have both phylogenetically stable and unstable gene ...[more]

PMID: 30586459

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Project description:BACKGROUND: The arylamine N-acetyltransferases (NATs) are a unique family of enzymes widely distributed in nature that play a crucial role in the detoxification of aromatic amine xenobiotics. Considering the temporal changes in the levels and toxicity of environmentally available chemicals, the metabolic function of NATs is likely to be under adaptive evolution to broaden or change substrate specificity over time, making NATs a promising subject for evolutionary analyses. In this study, we trace the molecular evolutionary history of the NAT gene family during the last ~450 million years of vertebrate evolution and define the likely role of gene duplication, gene conversion and positive selection in the evolutionary dynamics of this family. RESULTS: A phylogenetic analysis of 77 NAT sequences from 38 vertebrate species retrieved from public genomic databases shows that NATs are phylogenetically unstable genes, characterized by frequent gene duplications and losses even among closely related species, and that concerted evolution only played a minor role in the patterns of sequence divergence. Local signals of positive selection are detected in several lineages, probably reflecting response to changes in xenobiotic exposure. We then put a special emphasis on the study of the last ~85 million years of primate NAT evolution by determining the NAT homologous sequences in 13 additional primate species. Our phylogenetic analysis supports the view that the three human NAT genes emerged from a first duplication event in the common ancestor of Simiiformes, yielding NAT1 and an ancestral NAT gene which in turn, duplicated in the common ancestor of Catarrhini, giving rise to NAT2 and the NATP pseudogene. Our analysis suggests a main role of purifying selection in NAT1 protein evolution, whereas NAT2 was predicted to mostly evolve under positive selection to change its amino acid sequence over time. These findings are consistent with a differential role of the two human isoenzymes and support the involvement of NAT1 in endogenous metabolic pathways. CONCLUSIONS: This study provides unequivocal evidence that the NAT gene family has evolved under a dynamic process of birth-and-death evolution in vertebrates, consistent with previous observations made in fungi.

Dataset Information

Rapid birth-death evolution and positive selection in detoxification-type glutathione S-transferases in mammals.

Publications

Rapid birth-death evolution and positive selection in detoxification-type glutathione S-transferases in mammals.

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