balanced polymorphism

Ségurel L, Thompson EE, Flutre T, Lovstad J, Venkat A, Margulis SW, Moyse J, Ross S, Gamble K, Sella G, Ober C & Przeworski M 2012 The ABO blood group is a trans-species polymorphism in primates. PNAS 109:18493-18498.

  • that different species share the same two A/B alleles could be the result of convergent evolution in many lineages or of an ancestral polymorphism stably maintained for millions of years and inherited across (at least a subset of) species
  • the two possibilities have been debated for decades, with a consensus emerging that A is ancestral and the B allele has evolved independently at least six times in primates (in human, gorilla, orangutan, gibbon/siamang, macaque, and baboon)
  • the human A/B polymorphism arose more recently than the split with chimpanzee
  • we show instead that the remarkable distribution of ABO alleles across species reflects the persistence of an old ancestral polymorphism that originated at least 20 million years (My) ago and is shared identical by descent by humans and gibbons as well as among distantly related Old World monkeys
  • the selection mechanism maintaining this polymorphism across so many primate species is largely unknown
  • heterozygote advantage (seen e.g., in the HBB gene in response to malaria and sickle-cell anemia) (32), may be unlikely to underlie long-lived balancing selection, instead representing a transient solution to balancing selection pressures until a single allele that confers the heterozygote phenotype arises or a duplication occurs
  • the AB phenotype can be created by single "cis-AB" alleles
  • yet such alleles have not reached fixation in any of the surveyed species and are rare in humans
  • the selected phenotype is probably not tied to the expression of antigens on red blood cells, a trait restricted to hominoids
  • these histo-blood labels are unlikely to provide a complete description of the allelic classes acted on by natural selection
  • variation at ABO reflects a multiallelic balanced polymorphism, with cryptic differences in function among A and B alleles