Background: The role of AID/APOBEC proteins in the mammalian immune response against retroviruses and retrotransposons is well established. G to A hypermutations, the hallmark of their cytidine deaminase activity, are present in several mammalian retrotransposons. However, the role of AID/APOBEC proteins in non-mammalian retroelement restriction is not completely understood.Results: Here we provide the first evidence of anti-retroelement activity of a reptilian APOBEC protein. The green anole lizard A1 protein displayed potent DNA mutator activity and inhibited ex vivo retrotransposition of LINE1 and LINE2 ORF1 protein encoding elements, displaying a mechanism of action similar to that of the human A1 protein. In contrast, the human A3 proteins did not require ORF1 protein to inhibit LINE retrotransposition, suggesting a differential mechanism of anti-LINE action of A1 proteins, which emerged in amniotes, and A3 proteins, exclusive to placental mammals. In accordance, genomic analyses demonstrate differential G to A DNA editing of LINE retrotransposons in the lizard genome, which is also the first evidence for G to A DNA editing in non-mammalian genomes.Conclusion: Our data suggest that vertebrate APOBEC proteins differentially inhibit the retrotransposition of LINE elements and that the anti-retroelement activity of APOBEC proteins predates mammals.
|State||Published - 17 Dec 2013|
Bibliographical noteFunding Information:
We thank Shai Carmi for his help at the early stage of the project, and Norihiro Okada, John Moran, Bryan Cullen, Boris Matija Peterlin, Rai Kunal, Silvestro Conticello and Yong-Hui Zheng for reagents. We thank Alenka Čopič for critical reading of the manuscript. This work was supported by the Slovenian Research Agency [31952 to NLi, J7-2230, J1-2141 to NLo and MB, J3-4168 to MB and P1-0207 to NLo and TP]. BAK and EYL were supported by the Israel Science foundation [728/10] and by the European Research Council . Funding for open access charge: 31952 to NLi.
- Cytidine deaminase
- G to A hypermutation
- Lizard APOBEC1
- Zebrafish APOBEC2
- Zebrafish LINE2