Reconstructing the evolutionary history of human, simian, and prosimian immunodeficiency viruses

Abstract

SummaryWhile paleovirological evidence supports the idea that the ancestors of modern simian (SIV) and prosimian (pSIV) immunodeficiency viruses have been evolving in nonhuman primates for millions of years, standard molecular clock methods calibrated using contemporary sequences significantly underestimate their times of origin. This discrepancy is attributed to the time-dependent nature of evolutionary rate estimates whereby the rate of virus evolution varies with respect to the time window of its measurement. While biogeographical calibrations may provide better estimates across intermediate timescales, there is currently no unifying framework that can allow inference of lentiviral ages across all relevant timescales. Here we showed that by correcting for such time-dependent rate effects using the recently developed Prisoner-of-War evolutionary model, we can successfully reconstruct the evolutionary history of human, simian, and prosimian immunodeficiency viruses across vastly different timescales and allowed estimates of the age of lineages that gave rise to HIV-1 and HIV-2. The model also predicted that the most recent common ancestor of SIV and pSIV lived around 21 million years ago, suggesting that the most likely explanation for the origins of primate lentiviruses is a terrestrial transfer of lentiviruses between African and Malagasy primates during the last episode of colonisation of Madagascar. Infections have entered via a land bridge in a group of mammals or through a nonprimate vector or transfer mediated by an aerial vector species. We also found that the most recent common ancestor of SIVs lived nearly a million years ago and that some SIV lineages codiverged with their hosts for several hundreds of thousands of years. The predicted long evolutionary timescales of SIVs and potential for close virus/host co-adaptation is consistent with their reduced or minimal pathogenicity in their native hosts, contrasting with the very recent evolutionary origins of highly pathogenic HIV strains in humans.