Monday, October 17, 2016

HPV Strain 16A Was Acquired Via Sex With Archaic Hominins

Every human suffers through life a number of papillomaviruses (PVs) infections, most of them asymptomatic. A notable exception are persistent infections 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 wanting. 
We have analysed extant HPV16 diversity and compared the evolutionary and phylogeographical patterns of humans and of HPV16. We show that codivergence 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. 
We propose that after out-of-Africa migration of modern human ancestors, sexual transmission between human populations introduced HPV16A into modern human ancestor populations. We hypothesise that differential coevolution of HPV16 lineages 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 may be largely responsible for the present-day differential prevalence and association with cancers for HPV16 variants.
Ville N. Pimenoff, Cristina Mendes de Oliveira, Ignacio G. Bravo. Transmission Between Archaic and Modern Human Ancestors During the Evolution of the Oncogenic Human Papillomavirus 16. Molecular Biology and Evolution (2016).

This scenario finally explains unsolved questions: why human diversity is largest in Africa, while HPV16 diversity is largest in East-Asia, and why the HPV16A variant is virtually absent in Sub-Saharan Africa while it is by far the most common one in the rest world. . . .  Since HPVs do not infect bones, current Neanderthal and Denisovan genomes do not contain HPVs. As a next step, the authors hope to trace HPVs sequences in ancient human skin remains as a more direct test of their hypothesis.

While diseases originating in other species are hardly new, a solid link between archaic admixture and a specific sexually transmitted disease that modern humans received from archaic hominins is unprecedented.

It is also in accord with existing archaic DNA evidence showing some level of admixture between Neanderthals and Denisovans which would have allowed whichever of the species harbored HPV16A (if they did not share it from a common ancestor) to bring it in the other species.

Also, given that archaic admixture took place ca. 50,000 to 75,000 years ago, while HPV16A is still killing tens of thousands, if not more, people each year, it demonstrates that immune response and natural selection are not all powerful, particularly in the case of relatively low lethality infections that often strike after someone has already reproduced.

This development also rekindles curiosity regarding disease exchange following first contact with archaic hominins in general. Did modern human diseases ravage archaic hominins in the way that European first contact with Native Americans did? Did the reverse happen, or were both species seriously impacted by the new diseases that they respectively encountered?

Usually, we assume that modern humans either outcompeted or killed off archaic hominins, or that climate and the like had already established an archaic hominin bottleneck, but new diseases could have similar effects, in most cases through intraspecies transmission of the new diseases even before first contact.

UPDATE October 19, 2016: Vox covers the story with more panache: "Neanderthals may have given us their genital warts. Gee, thanks. To be fair, we may have given them diseases that ultimately led to their extinction." by Brian Resnick.

UPDATE (October 31, 2016): John Hawks has an interesting follow up observation:
There is, by the way, the interesting question of whether Neandertal immune variants might influence susceptibility to the strain in question, which has made little inroad into sub-Saharan Africa.

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