ABO genetic variation in Neanderthals and Denisovans

Variation at the ABO locus was one of the earliest sources of data in the study of human
population identity and history, and to this day remains widely genotyped due to its
importance in blood and tissue transfusions. As one of the first genetic markers, variation
at the ABO gene has been studied for over 60 years, and yet there are some aspects of
its evolution that remain mysterious. Here, we look at ABO blood type variants in our
archaic relatives: Neanderthals and Denisovans. Our goal is to understand the genetic
landscape of the ABO gene in archaic humans, and how it relates to modern human ABO
variation. We analyze coding variation at the ABO locus from next-generation sequences
in ∼2,500 individuals from 28 populations, including three Neanderthal and one Denisovan
individuals. We use the modern human haplotypes to impute ABO genotypes for the four
archaic human genomes. We found that the Siberian Neanderthals, Altai and Chagyrskaya,
are both homozygous for a derived Neanderthal variant of the O allele, while the European
Neanderthal, Vindija, is a heterozygote for two derived Neanderthal variants, an O variant
different from Altai and Chagyrskaya, and a rare cis-AB variant. The Denisovan individual
is homozygous for an ancestral variant of the O allele, similar to variants found widely in
modern humans. Perhaps more surprisingly, the derived O allele variant found in the Altai
Neanderthal can be found at low frequencies in modern European and Southeast Asian
individuals, and the derived O allele variant found in the Vindija Neanderthal is also found
at very low frequency in East Asian individuals. Our genetic distance analyses suggests
both alleles were introgressed through Neanderthal-human gene flow. In summary, our
study identifies the genetic variation of the ABO gene in archaic humans, we find that
ABO allele diversity in Neanderthals was likely high, and that some of these alleles still
survive in modern humans due to inbreeding with Neanderthals.