Large-Scale DNA Editing of Retrotransposons Accelerates Mammalian Genome Evolution

Abstract

Retrotransposons had an important role in genome evolution, including the formation of new genes and promoters and the rewiring of gene networks. However, it is unclear how such a repertoire of functions emerged from a relatively limited number of source sequences. Here we show that DNA editing, an antiviral mechanism, accelerated the evolution of mammalian genomes by large-scale modification of their retrotransposon sequences. We find numerous pairs of retrotransposons containing long clusters of G-to-A mutations that cannot be attributed to random mutagenesis. These clusters, which we find across different mammalian genomes and retrotransposon families, are the hallmark of APOBEC3 activity, a potent antiretroviral protein family with cytidine deamination function. As DNA editing simultaneously generates a large number of mutations, each affected element begins its evolutionary trajectory from a unique starting point, thereby increasing the probability of developing a novel function. Our findings thus suggest a potential mechanism for retrotransposon domestication.