Blood groups of Neandertals and Denisova decrypted

Blood group systems were the first phenotypic markers used in anthropology to decipher the origin of populations, their migratory movements, and their admixture. The recent emergence of new technologies based on the decoding of nucleic acids from an individual’s entire genome has relegated them to their primary application, blood transfusion. Thus, despite the finer mapping of the modern human genome in relation to Neanderthal and Denisova populations, little is known about red cell blood groups in these archaic populations. Here we analyze the available high-quality sequences of three Neanderthals and one Denisovan individuals for 7 blood group systems that are used today in transfusion (ABO including H/Se, Rh (Rhesus), Kell, Duffy, Kidd, MNS, Diego). We show that Neanderthal and Denisova were polymorphic for ABO and shared blood group alleles recurrent in modern Sub-Saharan populations. Furthermore, we found ABO-related alleles currently preventing from viral gut infection and Neanderthal RHD and RHCE alleles nowadays associated with a high risk of hemolytic disease of the fetus and newborn. Such a common blood group pattern across time and space is coherent with a Neanderthal population of low genetic diversity exposed to low reproductive success and with their inevitable demise. Lastly, we connect a Neanderthal RHD allele to two present-day Aboriginal Australian and Papuan, suggesting that a segment of archaic genome was introgressed in this gene in non-Eurasian populations. While contributing to both the origin and late evolutionary history of Neanderthal and Denisova, our results further illustrate that blood group systems are a relevant piece of the puzzle helping to decipher it.

Lastly, our study highlights unfavorable characteristics that can lead to “demographic fragility”. This fragility can be evoked on the basis of two elements: a low genetic diversity and the possible presence of HDFN. Indeed, the large number of shared alleles by the four archaic genomes despite their geographical and temporal distribution may be related to the deduced inbreeding situation in Neanderthals [14–16, 58], known to be a source of low adaptability. Meanwhile, the Neanderthal RH allele variants encode for partial RhD, Rhc and Rhe antigens, only Denisova 3 presents a complete form in terms of epitopes, such as they are described in their “wild” forms in modern humans. Partial RhD, Rhc and Rhe antigens lacking epitopes may induce an immune response when exposed to complete antigens [59, 60]. Moreover, when the RHCE*ceEK allele is present in a double dose (a situation which may turn out to be frequent in view of its presence in the 3 Neanderthals), in addition to the presence of partial Rhc and Rhe antigens, it encodes a phenotype defined by the absence of an Rh antigen named RH18. Today, this antigen is considered to be a high frequency antigen in the modern human population. Thus, a Neanderthal mother with partial RhD, Rhc, and Rhe phenotypes and sometimes RH:-18, carrying a Denisovan foetus expressing complete forms of RhD, Rhc and Rhe antigens and expressing the RH18 antigen, would have been prone to be immune to missing epitopes and synthesize anti-RhD, anti-Rhc, anti-Rhe and even anti-RH18 antibodies. These antibodies are known to have an important clinical significance in terms of HDFN [32]. These elements could have contributed to weakening the descendants to the point of leading to their demise especially combined with the competition with Homo sapiens for the same ecological niche [61].

Citation: Condemi S, Mazières S, Faux P, Costedoat C, Ruiz-Linares A, Bailly P, et al. (2021) Blood groups of Neandertals and Denisova decrypted. PLoS ONE 16(7): e0254175. https://doi.org/10.1371/journal.pone.0254175