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There are three common alleles (A, B, and O) at the human ABO blood group locus. We compared nucleotide sequences of these alleles, and relatively large numbers of nucleotide differences were found among them. These differences correspond to the divergence time of at least a few million years, which is unusually large for a human allelic divergence under neutral evolution. We constructed phylogenetic networks of human and nonhuman primate ABO alleles, and at least three independent appearances of B alleles from the ancestral A form were observed. These results suggest that some kind of balancing selection may have been operating at the ABO locus. We also constructed phylogenetic trees of ABO and their evolutionarily related alpha-1,3-galactosyltransferase genes, and the divergence time between these two families was estimated to be roughly 400 MYA.

Evolution of primate ABO blood group genes and their homologous genes