Large-scale DNA editing of retrotransposons accelerates mammalian genome evolution

Shai Carmi, George M. Church, Erez Y. Levanon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

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.

Original languageAmerican English
Article number519
JournalNature Communications
Volume2
Issue number1
DOIs
StatePublished - 2011
Externally publishedYes

Bibliographical note

Funding Information:
This work is supported by the Israel Science foundation (grant number 728/10) and by IBM’s Smarter Planet Innovation Award. S.C. is supported by the Adams Program of the Israel Academy of Sciences and Humanities. We thank Reuben Harris for commenting on an early version of the manuscript.

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