Temme et al. (1) found that the Neanderthals and the HLA-DPB1*0401 shared Lys at the 69th amino acid and GGPM at the 84th to 87th amino acids of HLA-DPβ. They thus concluded that the Lys-69/GGPM-(84–87) in DPB1*0401 was derived from a Neanderthal introgression.
They observed that DPB1*0401 is rare in sub-Saharan Africans (SSA), which is consistent with the claim that the DPB1*0401 was from Neanderthal introgression. However, the DPB1*0402 also carries the Lys-69/GGPM-(84–87), and the frequency of DPB1*0401 and DPB1*0402 in SSA are 5.5 and 18.9%, respectively. Given that the SSA are nearly free from Neanderthal introgression (2), it is less likely that haplotypes from Neanderthal could reach a frequency as high as 24.4% in SSA.
Further, we reconstructed a phylogenetic tree for DPB1*0201, DPB1*0202, DPB1*0301, DPB1*0401, and DPB1*0402 haplotypes, along with chimpanzee and high coverage Neanderthal and Denisovan sequences. If the DPB1*0401 were from recent Neanderthal introgression, one would expect that it first coalesced with Neanderthal, instead of other modern human haplotypes (3). However, it was observed that the DPB1*0401 first coalesced with DPB1*0402, then with the two DPB1*02 haplotypes, and then with the Neanderthal and Denisovan sequences. Divergence time between DPB1*0401 and Neanderthal was estimated as 2200 thousand years ago (KYA) (95% confidence interval (CI): 1657.8–2742.2 KYA), which far predates the Neanderthal − modern human divergence time (∼270 KYA). This observation is also inconsistent with the hypothesis that the DPB1*0401 was from Neanderthal introgression. To summarize, the identified Neanderthal introgression at HLA-DPB1*0401 could be an artifact that resulted from ancient population structure.
References
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