Retroviruses drive the rapid evolution of mammalianAPOBEC3genes

Abstract

APOBEC3(A3) genes are members of theAID/APOBECgene family that are found exclusively in mammals.A3genes encode antiviral proteins that restrict the replication of retroviruses by inducing G-to-A mutations in their genomes and have undergone extensive amplification and diversification during mammalian evolution. Endogenous retroviruses (ERVs) are sequences derived from ancient retroviruses that are widespread mammalian genomes. In this study we characterize theA3repertoire and use the ERV fossil record to explore the long-term history of coevolutionary interaction between A3s and retroviruses. We examine the genomes of 160 mammalian species and identify 1,420AID/APOBEC-related genes, including representatives of previously uncharacterized lineages. We show thatA3genes have been amplified in mammals and that amplification is positively correlated with the extent of germline colonization by ERVs. Moreover, we demonstrate that the signatures of A3-mediated mutation can be detected in ERVs found throughout mammalian genomes and show that in mammalian species with expandedA3repertoires, ERVs are significantly enriched for G-to-A mutations. Finally, we show thatA3amplification occurred concurrently with prominent ERV invasions in primates. Our findings establish that conflict with retroviruses is a major driving force for the rapid evolution of mammalianA3genes.

Retrocopying expands the functional repertoire of APOBEC3 antiviral proteins in primates

“…Recent work corroborates the presence of A3 retrocopies in some genomes and suggests that the A3 content of mammalian genomes may be even more variable and dynamic than previously appreciated (Hayward et al, 2018;Ito et al, 2020). Our data suggests that A3 retrocopying is more prevalent in NWM genomes compared even to other simian primates.…”

“…Here, we investigated whether retrocopying may have similarly diversified another family of host defense genes: the APOBEC3 (A3) cytidine deaminases. Although the common ancestor of mammals likely encoded three A3 genes (Münk et al, 2012), this locus has recurrently expanded and contracted throughout mammalian evolution (Ito et al, 2020), including a dramatic expansion to seven paralogous genes in catarrhine primates (Old World monkeys and hominoids) followed by recurrent positive selection of this expanded gene set (Bulliard et al, 2009;Compton et al, 2012;Duggal et al, 2011;Henry et al, 2012;McLaughlin et al, 2016;OhAinle et al, 2006). We found that ancient and ongoing retrocopying has further diversified the already expansive A3 gene locus in primates.…”

Long-read sequencing reveals rapid evolution of immunity- and cancer-related genes in bats

“…Dynamic evolution of immune-related genes has played an important role in animal evolution 62,[81][82][83] , helping animals adapt to diverse pathogens. The expansion of IR-IFITM genes may reflect an evolutionary response to pathogen pressure in phyllostomid bats.…”

Characterization of the mechanism by which the RB/E2F pathway controls expression of the cancer genomic DNA deaminase APOBEC3B

“…The human APOBEC family has nine active family members: APOBEC1, AID, and APOBEC3A/B/C/D/F/G/H [reviewed by (Green & Weitzman, 2019;Harris & Dudley, 2015;Ito, Gifford, & Sato, 2020;Olson, Harris, & Harki, 2018;Silvas & Schiffer, 2019;Simon, Bloch, & Landau, 2015;Siriwardena, Chen, & Bhagwat, 2016)]. Although several APOBEC3s have been implicated in cancer mutagenesis including APOBEC3A (A3A) and APOBEC3H (A3H) (Chan et al, 2015;Nik-Zainal et al, 2014;Starrett et al, 2016;Taylor et al, 2013), a particularly strong case can be made for APOBEC3B (A3B).…”