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. 2021 Jul 29;38(8):3373-3382.
doi: 10.1093/molbev/msab109.

ABO Genetic Variation in Neanderthals and Denisovans

Fernando A Villanea  1   2 , Emilia Huerta-Sanchez  2 , Keolu Fox  3
Affiliations

ABO Genetic Variation in Neanderthals and Denisovans

Fernando A Villanea et al. Mol Biol Evol. .

Erratum in

Abstract

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. 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 found two Neanderthal variants of the O allele in the Siberian Neanderthals (O1 and O2), one of these variants is shared with an European Neanderthal, who is a heterozygote for this O1 variant and a rare cis-AB variant. The Denisovan individual is heterozygous for two variants of the O1 allele, functionally similar to variants found widely in modern humans. Perhaps more surprisingly, the O2 allele variant found in Siberian Neanderthals can be found at low frequencies in modern Europeans and Southeast Asians, and the O1 allele variant found in Siberian and European Neanderthal is also found at very low frequency in modern East Asians. Our genetic distance analyses suggest both alleles survive in modern humans due to inbreeding with Neanderthals. We find that the sequence backgrounds of the surviving Neanderthal-like O alleles in modern humans retain a higher sequence divergence than other surviving Neanderthal genome fragments, supporting a view of balancing selection operating in the Neanderthal ABO alleles by retaining highly diverse haplotypes compared with portions of the genome evolving neutrally.

Keywords: ABO blood group, population genetics; Denisovan; Neanderthal; archaic introgression.

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Figures

Fig. 1.
Fig. 1.
Archaic ABO haplotype sharing through time, and geographic location for three Neanderthal and one Denisovan individuals. The O2 allele found in the earlier Altai Neanderthal is found in modern humans in Europe and Southeast Asia. The Chagyrskaya Neanderthal presents the same O2 allele (but different haplotype background) and a O1 allele shared with the later Vindija Neanderthal, and found in modern humans East Asia. The Denisovan O variants are not directly shared with either Neanderthals or modern humans.
Fig. 2.
Fig. 2.
Annotated PHASE output for the 1,000 Genomes Project and archaic genomes; 114 unique haplotypes total. Lower-case bases indicate missing data in the archaic genomes imputed from the modern data.
Fig. 3.
Fig. 3.
Haplotype distances calculated in Haplostrips for the 1,000 Genomes Project populations, polarized relative to a consensus of the two archaic haplotypes: (top) Denisova, (bottom) Altai Neanderthal. Note that archaic haplotypes are unphased, and heterozygous alleles are randomly assigned between the two chromosomes.
Fig. 4.
Fig. 4.
Haplotype distances calculated in Haplostrips for the 1,000 Genomes Project populations, polarized relative to a consensus of the two archaic haplotypes: (top) Chagyrskaya Neanderthal, (bottom) Vindija Neanderthal. Note that archaic haplotypes are unphased, and heterozygous alleles are randomly assigned between the two chromosomes.
Fig. 5.
Fig. 5.
Contour density plots of match proportion of human-Neanderthal introgressed segments to the actual Vindija and Altai Neanderthal genomes. The plot visualizes the affinity of all Sprime inferred fragments to the Altai and Vindija Neanderthals (0 = completely different, 1 = identical to Neanderthal). The red x marks the human-Neanderthal introgressed ABO alleles found in (a) European and (b) Asian populations.
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