Ancient origin of the null allele se(428) of the human ABO-Secretor locus (FUT2)

Tn human populations, a null allele having several nucleotide differences f rom the wild-type allele is segregating at the FUT2 locus (the ABO-Secretor locus) encoding alpha(1,2)fucosyltransferase. To estimate the age of the m ost recent common ancestor (MRCA) of these two alleles, we sequenced FUT2 h omologues from chimpanzee, gorilla, orangutan, and green monkey. Since we d id not detect acceleration or any heterogeneity in the substitution rate at this locus among these species, the age of the MRCA was estimated to be ar ound 3 MYA, assuming the divergence time of human and chimpanzee to be 5 MY A. We developed a simple test to examine whether or not the old age of the MRCA of the FUT2 is consistent with that expected for two divergent neutral alleles sampled from a random mating population. An application of the tes t to the data at FUT2 indicated that the age of the MRCA is too old to be e xplained by the simple neutral assumptions, although our test depends on ac curate estimation of the divergence time of human and chimpanzee in units o f twice the human population size. Various possibilities including balancin g selection are discussed to explain this old age of the MRCA.