Fig 8. Schematic illustration of HPV16 codivergence with archaic hominins.

The model was based on HPV16 variant divergence time estimation, phylogenetic topology, and geographic distribution that superimposes an ancestral viral transmission between Neanderthals/Denisovans and modern human populations. The early divergence event among deeply separated HPV16 variant lineages (A vs. BCD) suggests ancient virus-host codivergence following the speciation of modern humans and archaic hominins (e.g., Neanderthals and Denisovans) from their most recent common ancestors. The gene flow through host interbreeding between archaic hominins allowed viral transmission from Neanderthals/Denisovans to modern humans. t_h-n/d denotes the splitting time between Neanderthals/Denisovans and modern humans, t_h represents the speciation of modern humans. t_af indicates the era of population expansion of modern humans walking out-of-Africa. t_g indicates the time of gene flow (f) that may have occurred between modern humans and Neanderthals/Denisovans. t_n estimates the extinction of Neanderthals/Denisovans. The arrows indicate the out-of-Africa migration events of archaic and modern human populations. The broken lines indicate potential extinction of viral variants. Branch lengths and widths are not drawn to scale.