A (mysterious) genetic link between Neanderthals and Australia

Analyses of blood group systems of Neanderthals and Denisovans contributed to a better understanding of their origin, expansion and encounters with Homo sapiens. Blood group profiles revealed polymorphism at the ABO locus, ancestral and African-origin alleles, and a RH haplotype presently secluded in Oceania, plausible relic of introgression events into modern humans prior their expansion towards Southeast Asia. An additional contribution is the reduced variability of many alleles and the possible presence of haemolytic disease of the foetus and new-born, which reinforces the notion of high inbreeding, weak demography and endangered reproductive success of the late Neanderthals, giving to our species the great opportunity to spread throughout the world.

The new partial RHD allele, RHD*DIII type4 with c.602G and c.733C, reported in the three Neanderthal individuals, and not in Denisova 3, was unknown in modern humans until 2019 and its description as a new variant in an individual from the First Nation of Australia with a RHD Exon-9 deletion or rearrangement with RHCE Exon-9 [29]. Thus, this polymorphism is not a new variant in the historical sense of the term, as it was already present around 100 kya in Neanderthals. This result fuels the discussion about admixture events between the different lineages and also about the early dispersal of Homo sapiens via the Arabian Peninsula [44] towards Australia [45] and Oceania [46]. In order to assess whether the Neanderthal RHD*DIII type4 with c.602G and c.733C arose in modern humans from shared ancestry or introgression, we have modelled high-coverage modern chromosomes from Asia and Oceania (HGDP-CEPH collection, publicly available, [47]) as a mosaic of modern and archaic states using a hidden-Markov model (see S2 File for detailed methods). We found a probable introgressed tract of 15.7 Kb spanning over 4 exons of RHD in 5 individuals: 2 HGDP-Brahuis and 3 HGDP-Sepik Papuans (Fig 4). The 3 Sepik Papuans are heterozygous carriers of the derived allele at rs150073306 which defines the DUC2 allele (raising thus the MAF of the derived allele nearly to 19% in that population—see S2 File), for which Altai is homozygous. When phased, there is an almost identical haplotype to Altai and the Australian Aborigine in Papuan HGDP00546. A parsimonious hypothesis to explain the relic of a RHD haplotype common amongst all Neanderthals in 2 modern Oceanians only, would suggest that the RHD*DIII type4 with c.602G and c.733C profile have been carried by Levantine Neanderthals and passed to modern humans before 65 kya and the route towards SouthEast Asia [48, 49]. This assumption remains however speculative as the archaic tract was called at a low confidence level (>20%). A shorter tract (4.6Kb) was still called at a confidence level of >50% but not at higher confidence thresholds (>90%). Further analyses would be required to validate our assumption.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254175