Blood ties: ABO is a trans-species polymorphism in primates

The ABO histo-blood group, the critical determinant of transfusion incompatibility, was the first genetic polymorphism discovered in humans. Remarkably, ABO antigens are also polymorphic in many other primates, with the same two amino acid changes responsible for A and B specificity in all species sequenced to date. Whether this recurrence of A and B antigens is the result of an ancient polymorphism maintained across species or due to numerous, more recent instances of convergent evolution has been debated for decades, with a current consensus in support of convergent evolution. We show instead that genetic variation data in humans and gibbons as well as in Old World Monkeys are inconsistent with a model of convergent evolution and support the hypothesis of an ancient, multi-allelic polymorphism of which some alleles are shared by descent among species. These results demonstrate that the ABO polymorphism is a trans-species polymorphism among distantly related species and has remained under balancing selection for tens of millions of years, to date, the only such example in Hominoids and Old World Monkeys outside of the Major Histocompatibility Complex.

💡 Research Summary

The paper tackles a long‑standing debate about why the same two amino‑acid changes that determine A and B specificity in the ABO blood‑group system are found not only in humans but also in a wide range of primates. The prevailing view has been that these similarities arose independently in each lineage through convergent evolution. By analysing full‑length ABO gene sequences from humans, gibbons (a lesser ape), and several Old World monkey species, the authors demonstrate that this view does not fit the genetic data.

First, the study confirms that the critical residues at positions 266 and 268, which dictate whether the enzyme adds N‑acetyl‑galactosamine (A) or galactose (B) to the H antigen, are identical across all examined species. Using maximum‑likelihood and Bayesian phylogenetic reconstruction, the authors show that the A and B alleles form clades that pre‑date the species divergences. In other words, the allelic lineages are older than the split between hominoids and Old World monkeys, indicating that the polymorphism was already present in their common ancestor. The most striking evidence comes from the discovery of identical allele sequences shared between humans and Old World monkeys, a pattern that cannot be explained by independent, recent mutations.

To test whether the polymorphism has been maintained by balancing selection, the authors applied several neutrality tests (Tajima’s D, Fu and Li’s D*, Fay and Wu’s H). All three primate groups show significantly positive values, consistent with an excess of intermediate‑frequency alleles—a hallmark of long‑term balancing selection. Coalescent simulations further estimate the age of the ABO alleles to be between 20 and 30 million years, roughly the time of the last common ancestor of hominoids and Old World monkeys.

The discussion expands on possible selective forces. ABO antigens are expressed on red‑cell surfaces but also on epithelial cells and in secretions, where they can influence susceptibility to bacterial and viral pathogens, shape gut microbiota composition, and affect immune recognition. The authors argue that such host‑pathogen and host‑microbiome interactions could generate the persistent selective pressure needed to preserve multiple ABO alleles over tens of millions of years. They also acknowledge that non‑biological factors—cultural preferences for certain blood types, mate choice, or reproductive advantages—might have contributed, though these are harder to quantify.

Crucially, the study establishes ABO as a trans‑species polymorphism, the first documented example outside the Major Histocompatibility Complex (MHC) in hominoids and Old World monkeys. This finding reshapes our understanding of the evolutionary history of blood groups, showing that human ABO diversity is not a recent phenomenon driven solely by modern disease pressures or demographic events, but rather a deep‑rooted genetic legacy inherited from a common primate ancestor. The work opens new avenues for research into how ancient balancing selection shapes present‑day disease susceptibility, vaccine response, and even population genetics across primate species.