Evolution of the O alleles of the human ABO blood group gene.

BACKGROUND To date, at least 40 different alleles O have been characterized on the basis of exon 6 and exon 7 sequences but not always for intron 6. STUDY DESIGN AND METHODS Among 415 individuals, from four continents (Africa, Europe, South America, and Asia), studied for exon 6 and exon 7 sequences, we selected 46 individuals (of respective phenotypes O [39], AB [3], B [3], or A [1]) for sequencing 1800-bp amplicons spanning exon 6, intron 6, and exon 7. The amplicons were characterized either by direct sequencing or after cloning when required. RESULTS We defined 14 new intron 6 O allele sequences, including four recombinant alleles. Based on sequence comparison, a phylogenetic network was constructed. It confirmed recombinant allele origins and that most O alleles are derived by point mutations from the two worldwide distributed alleles O01 and O02. CONCLUSION Allele O phylogenetic analysis suggests that the most frequent silencing mutation (deletion of a G in exon 6) appeared once in human evolution in the ancient O02 allele lineage and that allele O01 resulted from an interallele exchange between O02 and A101. Assuming constancy of evolutionary rate, diversification of the representative alleles of the three human ABO lineages (A101, B101, and O02) was estimated at 4.5 to 6 million years ago.