Every human suffers through life with a number of papillomaviruses (PVs) infections, most of them asymptomatic. One notable exception is persistent infection by Human Papillomavirus-16 (HPV16), the most oncogenic infectious agent for humans and responsible for most infection-driven anogenital cancers. Oncogenic potential is not homogeneous among HPV16 lineages, and genetic variation within HPV16 exhibits some geographic structure. However, an in-depth analysis of the HPV16 evolutionary history is still badly needed.
Authors of the Mol Biol Evol article have analysed surviving HPV16 diversity and compared the evolutionary and phylogeographical patterns of humans and of HPV16. They found that co-divergence with modern humans explains at most 30% of the present viral geographical distribution. The most explanatory scenario suggests that ancestral HPV16 already infected ancestral human populations, and that viral lineages co-diverged with the hosts in parallel with the split between archaic Neanderthal-Denisovans and ancestral modern human populations, generating the ancestral HPV16A and HPV16BCD viral lineages, respectively.
Authors thus propose that after Out-of-Africa migration of modern human ancestors, sexual transmission between human populations introduced HPV16A into modern human ancestor populations. They hypothesise that differential co-evolution of HPV16 lineages occurred––with different, but closely related, ancestral human populations and subsequent host-switch events in parallel with introgression of archaic alleles into the genomes of modern human ancestors. This co-evolution may be largely responsible for the present-day differential prevalence and association with cancers caused by particular HPV16 variants.
Today’s genital warts came from trysts between Neanderthals and Homo sapiens
Sometimes evolution gets really awkward
Genital warts, or human papillomavirus (HPV), isn’t just a disease of the modern world and its newfangled sexual mores. In fact, various strains of HPV plagued our ancestors long before Homo sapiens evolved. A new study in Molecular Biology and Evolution reveals that when the ancestors of Neanderthals and Denisovans left Africa over 500,000 years ago, they were already carrying a variant of HPV. The early humans who remained in Africa had their own variants of HPV, too. As the two populations evolved, their cancer-causing wart viruses evolved with them–until that fateful moment when Homo sapiens and Neanderthal came together, as it were.
Humans started having sex with Neanderthals over 100,000 years ago
A group of researchers in France and Spain used a common statistical modeling method to trace the evolutionary origins of today’s HPV. By looking at mutated regions in the virus, which occur regularly over time, the researchers discerned that HPV’s origins go back almost half a million years. The question was, how did various strains of HPV (including the extremely carcinogenic HPV16) make their way around the world? Currently, we see almost no HPV16 in Sub-Saharan Africa, while it’s incredibly common elsewhere.
The researchers had two working assumptions: either early humans brought HPV with them out of Africa, and new strains evolved in populations that split off from each other outside Africa; or early humans acquired the ancestral strain of HPV16 from Neanderthals and Denisovans they encountered. After modeling the likelihood of different scenarios, the researchers concluded that the latter fit the facts. They write:
The split between Neanderthals/Denisovans and modern human ancestor populations was mirrored by a split in the viral populations, namely HPV16A, carried by ancestral human populations, and HPV16BCD, carried by the populations of modern human ancestors in Africa… Later, the interbreeding events between Neanderthal and Denisovan populations with modern human ancestor populations lead to a host-switch through sexual transmission of the HPV16A virus lineage from archaic populations into the modern human ancestors. The HPV16A lineage, thus transmitted, expanded rapidly in the new host populations and became dominant in Eurasia and in the Americas.
Basically, when early humans left Africa 60-120,000 years ago, they already carried with them a few variants of HPV. Some of those variants remained behind in African populations and are still there today. One variant came with the migrating populations into Eurasia. But HPV16A, the ancestor of today’s dangerous and widely prevalent HPV16, came from Neanderthals and Denisovans. Early humans who had sex with Neanderthals and Denisovans were infected with this variant of genital warts, and over time their unprotected archaic human sex spread a sexually-transmitted infection throughout most of the world’s Homo sapiens population.
This lends further credence to the hypothesis that the Pleistocene was packed with hominin hanky-panky. The new research also underscores a basic lesson that we’ve all been taught in the 21st century: always practice safer sex, even if you’re getting down with a Denisovan.