In conclusion, we propose that the ancestral H2′ haplotype arose in eastern or central Africa and spread to southern Africa before the emergence of anatomically modern humans...Approximately 2.3 million years ago, the inversion rearranged to what we now refer as the direct orientation haplotype (H1′). This haplotype spread throughout the Homo ancestral populations in the African continent, virtually replacing the H2′ haplotype and becoming the predominant haplotype. We note that both the Denisova and Neandertal sister groups are predicted to have H1′ haplotypes...These early haplotypes were much simpler in their duplication architecture, similar to the patterns seen in great apes. We find that the more complex duplication architectures are particularly enriched in populations that migrated out of Africa. On the basis of sequence at the duplication loci, we estimate that the H2-specific duplication event occurred approximately 1.3 million years ago. Independent of the H2 duplication, the H1-specific duplication event occurred much more recently, approximately 250,000 years ago. Notably, we did not observe this haplotype in any of the African or Asian populations studied, suggesting that it may have been lost in these groups as a result of genetic drift. The H2D haplotype has risen to frequencies of 10–25% in European populations with virtually no genetic variation, suggesting an extremely recent and rapid expansion of this haplotype. High-coverage sequencing of more individuals along with fecundity data will likely shed further light on whether the high frequency of the haplotype-specific duplication in Europeans is due to selection or the effects of demographic history specific to this locus.
H2D individuals are susceptible to disease. If there is a fitness gain, there is also a loss. Despite his eugenical enthusiasms W. D. Hamilton ultimately gave up on the idea because he admitted it was difficult to predict what was beneficial and what is deleterious. Context matters. The distribution of haplotypes in this region seems to reflect echoes of deep pre-"Out of Africa" history in our species.