Dating the age of the SIV lineages that gave rise to HIV-1 and HIV-2

Abstract

Great strides have been made in understanding the evolutionary history of simian immunodeficiency virus (SIV) and the zoonoses that gave rise to HIV-1 and HIV-2. What remains unknown is how long these SIVs had been circulating in non-human primates before the transmissions to humans. Here, we use relaxed molecular clock dating techniques to estimate the time of most recent common ancestor for the SIVs infecting chimpanzees and sooty mangabeys, the reservoirs of HIV-1 and HIV-2, respectively. The date of the most recent common ancestor of SIV in chimpanzees is estimated to be 1492 (1266-1685), and the date in sooty mangabeys is estimated to be 1809 (1729-1875). Notably, we demonstrate that SIV sequences sampled from sooty mangabeys possess sufficient clock-like signal to calibrate a molecular clock; despite the differences in host biology and viral dynamics, the rate of evolution of SIV in sooty mangabeys is indistinguishable from that of its human counterpart, HIV-2. We also estimate the ages of the HIV-2 human-to-human transmissible lineages and provide the first age estimate for HIV-1 group N at 1963 (1948-1977). Comparisons between the SIV most recent common ancestor dates and those of the HIV lineages suggest a difference on the order of only hundreds of years. Our results suggest either that SIV is a surprisingly young lentiviral lineage or that SIV and, perhaps, HIV dating estimates are seriously compromised by unaccounted-for biases.

Figure 1. Maximum clade credibility trees.

SIVsm/HIV-2 loci (A) gag, (B) pol, and (C) env and SIVcpz/HIV-1 loci (D) gag, (E) pol, and (F) env are depicted. SIV lineages are blue, HIV-2 lineages are green, and HIV-1 lineages are red. Major SIVsm clades are designated by number and the HIV clades are designated by group. Nodes with posterior probability >0.9 are indicated with an asterisk.

Figure 2. Maximum likelihood phylogeny of SIV/HIV env locus.

SIVsm/HIV-2 lineages are green and their MRCA is designated with an open green star. SIVcpz/HIV-1 lineages are red and their MRCA is designated with a closed red star. All other SIV lineages are blue. Tree is midpoint rooted. Nodes with bootstrap support >80% are indicated with an asterisk.