Conservation and Innovation of APOBEC3A Restriction Functions during Primate Evolution.

Autor:	McLaughlin RN Jr; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA hsmalik@fhcrc.org., Gable JT; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA., Wittkopp CJ; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA Department of Microbiology, University of Washington, Seattle., Emerman M; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA., Malik HS; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA hsmalik@fhcrc.org.
Jazyk:	angličtina
Zdroj:	Molecular biology and evolution [Mol Biol Evol] 2016 Aug; Vol. 33 (8), pp. 1889-901. Date of Electronic Publication: 2016 Apr 06.
DOI:	10.1093/molbev/msw070
Abstrakt:	LINE-1 (long interspersed element-1) retroelements are the only active autonomous endogenous retroelements in human genomes. Their retrotransposition activity has created close to 50% of the current human genome. Due to the apparent costs of this proliferation, host genomes have evolved multiple mechanisms to curb LINE-1 retrotransposition. Here, we investigate the evolution and function of the LINE-1 restriction factor APOBEC3A, a member of the APOBEC3 cytidine deaminase gene family. We find that APOBEC3A genes have evolved rapidly under diversifying selection in primates, suggesting changes in APOBEC3A have been recurrently selected in a host-pathogen "arms race." Nonetheless, in contrast to previous reports, we find that the LINE-1 restriction activity of APOBEC3A proteins has been strictly conserved throughout simian primate evolution in spite of its pervasive diversifying selection. Based on these results, we conclude that LINE-1s have not driven the rapid evolution of APOBEC3A in primates. In contrast to this conserved LINE-1 restriction, we find that a subset of primate APOBEC3A genes have enhanced antiviral restriction. We trace this gain of antiviral restriction in APOBEC3A to the common ancestor of a subset of Old World monkeys. Thus, APOBEC3A has not only maintained its LINE-1 restriction ability, but also evolved a gain of antiviral specificity against other pathogens. Our findings suggest that while APOBEC3A has evolved to restrict additional pathogens, only those adaptive amino acid changes that leave LINE-1 restriction unperturbed have been tolerated. (© The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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