Human herpesvirus (HHV-6) has to haplotypes, A-6 and B-6, interestingly the virus can merge into human genes, blending into our DNA (the scientific term is that it "can integrate into the germline"). Roughly 1% of the global population (around 80 million people) carry the DNA of this virus inside one of their chromosomes, in each of the cells of their bodies. Scientists have asked themselves if this "integration" is ancient, or recent, and if it is still happening as people get infected with the virus.
Roughly 90% of humans are seropositive to HHV-6B, because as infants we are exposed to the virus (Roseola Infantum, also known as the Sixth Disease).
Research by Aswad A, et al. (2021) (Evolutionary History of Endogenous Human Herpesvirus 6 Reflects Human Migration out of Africa. Mol Biol Evol. 2021 Jan 4;38(1):96-107. doi: 10.1093/molbev/msaa190. PMID: 32722766; PMCID: PMC7782865.) explored the history of the virus and its "integration".
The "integrated" virus, which forms part of the chromosome, is passed on to the offspring of carriers, and this inherited chromosomally integrated HHV-6 (iciHHV-6). If the integration was ancient, it was passed down along thousands of generations in a parents-to-children line.
The inherited-integrated iciHHV-6 has been found in several chromosomes like number 17 and 22.
Aswad et al., built a phylogenetic tree of the circulating HHV-6 variants A and B (that cause Roseola) and the integrated virus snips inside human chromosomes. The authors state that "the ancestral circulating strains that resulted in these particular independent integration events are not among the known currently circulating strains sampled here. Similarly, the integrated HHV-6A is not acting as a reservoir for ongoing production of circulating strains... In contrast to HHV-6A, the tree for HHV-6B revealed a more entangled topology between circulating and endogenous genomes..."
They found that some clades mirror geographic origin: "among the iciHHV-6A sequences, we observed that individuals from clades A2 and A4 are exclusively European or North American... HHV-6B clades B3–6 and B8 are similarly homogenous and likely represent orthologous integrations in white Europeans and North Americans (and one Australian). This suggests that for each of these clades, those now carrying the virus share a common ancestor who was also European, and thus the virus integration event occurred prior to the diaspora of ancestors of these individuals; the virus thus likely integrated before the colonial era."
"our analysis also revealed a previously unidentified Native American carrier of iciHHV-6B, who possesses an HHV-6B sequence distinct from the other North American samples. Instead, this sequence is almost identical to the iciHHV-6B genome of a Maasai Kenyan sequence uncovered through our SRA mining, and a previously identified Pakistani sample (Zhang et al. 2017) (figs. 2 and 4)."
They then explain how this rare shared variant appeared in America, Asia, and Africa, a Native American who shares "integrated" sequence with a Kenyan and a Pakistani!:
"Unlike the ancestral European integrations, the last common ancestor of these individuals would have been before humans migrated out of Africa (50–100,000 years ago). The observation that they also resolve near the base of the tree further supports this interpretation, as does the fact that the most closely related sequence outside this clade is a circulating strain isolated from a Ugandan patient..."
By "resolve near the base of the tree" they mean that this specific branch is close to the root, and therefold, older than the other branches. As it is similar to the strain of an African (Ugandan), the Out of Africa logic suggests that the root of the tree is based in Africa. Below is the tree and this branch is highlighted.
However, as you can see in the image, not only is a "similar African" strain located at the root, there are three other Ugandan and three D.R.Congo subjects there too, all black-Africans but... one, closest to the root, is a WHITE NY U.S.A. sample!
The authors propose that an ancient ancestor in the distant past (~100 ky ago) before humans left Africa, underwent this "integration" of the virus into one of his or her chromosomes, and this bit of DNA passed on, unscathed, through countless generations, ending up in a Native American, a Pakistani, and a Kenyan Maasai. The tree below is Fig. 4 B, in their paper:
The age of this "integration" was estimated "to be ∼85,000–342,000 years old (depending on the mutation rate used)." Then it says "The Native American is a reference individual used in a South American study on the influences on physical appearance (Chacon-Duque et al. 2018)" Chacón-Duque's paper says that they "examined data for over 500,000 autosomal SNPs typed in more than 6,500 individuals born in Brazil, Chile, Colombia, Mexico and Peru." So, it does include Mexicans, from North America, and the rest of the samples are from South America. Notice that there was only one (1) sample in 6,500 who carried this integrated variant of HHV-6B. A very low frequency indeed!
The data used by Chacon-Duque also noted a high prevalence of African genes (slave trade) in Latin Americans: "~22% of the individuals studied show more than 5% sub-Saharan African ancestry." Which backs my suggestion of African introgression in the Native American sample of "integrated" HHV-6B .
Discussion
The Native American sample's origin isnt' clear in the paper, in one part it says that this sample differs from "the other North American samples", implying that it is North American.
The idea is interesting. However, considering all the bottlenecks that Amerindians have gone through including the founding effect of Beringia, and the loss of 90% of the Native American DNA due to disease, and strife during the conquest and discovery period 1492-1700s, it is difficult to believe that a trait that is now only found in 1% of human beings, managed to survive among Native Americans.
That it is shared by Old World people like the Maasai and the Pakistani could be possible, but the Amerindian carrying this genetic material seems to stretch the odds. Furthermore, no signs of this unique integration is found in Europe or the rest of Asia. What happened to those who carried the gene into Pakistan, and across Asia into America? They left no descent?
Could it be possible that an escaped African slave brought by the Portuguese or Spaniards to South America admixed with natives and passed on this chunk of HHV "integrated" into one of his genes?
It seems a more reasonable explanation.
The tree branch that holds all three samples shows that the closest to the root is the Pakistani, followed by the Amerindian and then, the Kenyan. Shouldn't the Kenyan be closer to the African root?
What is interesting is how the data is "adapted" to the preconceptions of an OOA move some 50-100 kya. Shouldn't the data independently show if that date is correct? Notice the wide window they calculated, a four-fould spread between lower and upper limits" ∼85,000–342,000 years old (depending on the mutation rate used).
It could have originated outside of Africa: We could also imagine a scenario where a Homo antecessor living in Eurasia 700,000 years ago, picked up the virus and it "integrated" into one of its chromosomes, his descent spread Denisovans and Neanderthals, and from there admixing with a modern humans ended up in Pakistan and America, and others crossing Gibraltar (see this post) reintroduced it into Africa. Somehow it didn't survive among those who would later become Europeans, and if these migrants took a northern route, it could have also avoided Eastern and Southern Asians, leaving no trace there.
It could have originated earlier among H. erectus and spread back into Africa with them, and possibly into America in an ancient peopling wave 500,000 years ago. Much later, once modern humans left Africa they could have intermixed in Pakistan, and (no need for them to carry it across Beringia), mated with H. erectus who carried the "integrated" virus, in America.
There are no records of "integrated" virus in ancient Amerindian (or Old World) samples. These would be important as they could help clarify the migration patterns of the virus inside our ancestors' chromosomes.
Let's see what future research discovers.
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