Tracking the history of HIV back to chimpanzees: is the evidence in the West African genome?

Papers explored in earlier STI blogs have traced the distribution through the world of the different HIV subtypes (https://blogs.bmj.com/sti/2013/01/04/reading-the-history-of-the-progress-of-the-hiv-epidemic-through-the-evidence-of-hiv-subtype-distribution/?q=w_sti_blog_sidetabhttp://sti.bmj.com/content/87/2/101.full?sid=2b7658a8-4f84-4d8a-b2bc-d5104c523180), and have used this information to track the origins of HIV-AIDS in central/western Africa probably at the beginning of the last century (http://journals.lww.com/aidsonline/pages/results.aspx?k=Tatem%20AND%20Salemi&Scope=AllIssues&txtKeywords=Tatem%20AND%20Salemi).  Now a research article published in Evolutionary Biology – Zhao, Roca et al. – has attempted to take back the story a further stage to the crossing of the species barrier and before (http://www.biomedcentral.com/1471-2148/12/237/abstract). Certainty in these matters is impossible; but Zhao, Roca et al. develop an interesting hypothesis based on genetic evidence – which is as follows.

Their point of departure is that transmission of the virus from the common chimpanzee to humans must have taken place at least four times, since the four principal HIV-1 strains present in humans (M, N, O, P) are closer in genetic sequence to strains of SIV, the chimpanzee form of HIV, than they are to the various HIV-1 sub-groups (A,B,C etc.) that derive from  strain M. On this basis, the authors hypothesize that, given the existence of SIV strains for 20,000 years, if the virus crossed the species barrier four times (between 1884 and 1924), in all probability it crossed it repeatedly over the centuries, but failed to generate persistent outbreaks in humans before the appearance of large cities.  If this hypothesis is correct, then genomic “signatures” in the chromosomes of the descendants of the affected populations ought to reflect the generation of selection pressure in these populations for resistance to SIV/HIV.

Among the diverse populations intensively genotyped as part of the human genome diversity panel are the Biaka Western Pygmies of the Central African Republic who have always resided within range of the SIV infected common chimpanzee.  The researchers seek genetic evidence for selection among the Biaka, by running pairwise genomic comparisons between the Biaka and four other central African peoples (including the Mbuti Eastern Pygmies, who are genetically close to the Biaka, but have always lived out of range of SIV infected chimpanzees).  They look for regions of the genome that: 1. signal strong selection pressure, and 2. have been associated with HIV-1 by various kinds of studies.

What they find is that of the ten possible pairwise comparisons between the five peoples, five comparisons detect regions with strong selection associated with HIV.  These involved CUL5, TRIM5, PARD3B and TSG101 which are detected as under strong selection eight times across the pairwise comparisons.  Seven out of the eight involve the Biaka.  The probability that randomly drawn genes would overlap seven or more signals of selection in a single population is reckoned by the authors at 0.05.  For the purposes of this analysis the researchers exclude from consideration host-genes associated with HIV that are below a genome-wise significance p<5×108.  Where this restriction is lifted a total of eight genomic regions are specified as showing protective variants.

On the basis of this evidence the authors consider their hypothesis that SIV/HIV has shaped the genomes of some west central African populations as worthy of further investigation.

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