Abstract
Host genomes have adopted several strategies to curb the proliferation of transposable elements and viruses. A recently discovered novel primate defense against retroviral infection involves a single-stranded DNA-editing enzyme, APOBEC3G, that causes hypermutation of HIV. The HIV-encoded virion infectivity factor (Vif) protein targets APOBEC3G for destruction, setting up a genetic conflict between the APOBEC3G and Vif genes. This kind of conflict leads to rapid fixation of mutations that alter amino acids at the protein–protein interface, referred to as positive selection. We show that the APOBEC3G gene has been subject to strong positive selection throughout the history of primate evolution. Unexpectedly, this selection appears more ancient than, and is likely only partially caused by, modern lentiviruses. Furthermore, five additional APOBEC genes in the human genome appear to be engaged in similar genetic conflicts, displaying some of the highest signals for positive selection in the human genome. Despite being only recently discovered, editing of RNA and DNA may thus represent an ancient form of host defense in primate genomes.
Highlights
Mobile genetic elements have been in conflict with host genomes for over a billion years
We find that APOBEC3G has been under remarkably strong positive selection, and has undergone several episodes of adaptive evolution throughout the history of primates
We report evidence for strong positive selection acting on a majority of the apolipoprotein B–editing catalytic polypeptide (APOBEC) genes, suggesting that this family of genes may have expanded in primate genomes for genome defense via RNA/DNA editing
Summary
Mobile genetic elements have been in conflict with host genomes for over a billion years. Representative examples of pairwise (sliding window) comparisons of Ka/Ks ratios between two hominids, two OWMs, and two NWMs suggest that the same domain of APOBEC3G has not been subject to positive selection throughout primate evolution (Figure 3A–3C). When the APOBEC3G gene is divided into structural domains, we find that all domains, including the active site domains, have undergone multiple distinct episodes of positive selection (Figure S1) This highly unusual pattern suggests that the genetic conflicts that have shaped APOBEC3G evolution have involved episodic protein–protein interactions with different parts of the entire APOBEC3G protein. Other studies have investigated a possible inhibitory role of other APOBEC genes but found that only APOBEC3G and APO-
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