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.
Human genetic variation in the ABO gene is a classic marker for genetic diversity in humans [Cavalli-Sforza et al., 1964]. Here, we provide an in-depth description of the genetic diversity of the ABO gene in four archaic humans, based on published ancient genomes. We found that archaic ABO haplotypes are polymorphic at the same positions which define modern human ABO function, and have posited that these archaic alleles must function similarly to modern human alleles. Furthermore, we found Denisovan-specific O alleles, which are genetically similar to modern O alleles, while Neanderthal-specific O alleles are derived relative to human alleles, but found today at low frequencies due to past humanNeanderthal admixture. Finding four different Neanderthal variants in late-era Neanderthals is unexpected. A common perception, based on long runs of homozygosity seen across Neanderthal genomes, is that late-era Neanderthals were extremely inbred and thus had reduced genetic diversity. The high allele diversity found in these Neanderthals was possibly maintained through balancing selection at the ABO locus. This notion dovetails with our contour map results, showing introgressed Neanderthal O haplotypes falling outside of the genome divergence of all other fragments, and suggests that balancing selection operated in Neanderthals similarly to modern humans.
I have previously highlighted the significance of the cis-AB allele here:
