Carmi, ShaiChurch, GeorgeLevanon, Erez Y.2021-10-042011-11-01Carmi, Shai, George Church, Erez Y. Levanon. "Large-Scale DNA Editing of Retrotransposons Accelerates Mammalian Genome Evolution." Nature Communications 2, no. 1 (2011): 519. DOI: 10.1038/ncomms15252041-1723https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37369662Retrotransposons 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.en-USJournal Article2017-08-0820112021-10-0410.1038/ncomms1525