BACKGROUND:To date, at least 40 different allelesOhave 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 6Oallele sequences,including four recombinant alleles. Based on sequence comparison, a phylogenetic network was constructed. It confirmed recombinant allele origins and that mostOalleles are derived by point mutations from the two worldwide distributed allelesO01andO02.CONCLUSION:AlleleOphylogenetic analysis suggests that the most frequent silencing mutation (deletion of a G in exon 6) appeared once in human evolution in the ancientO02allele lineage and that alleleO01resulted from an interallele exchange betweenO02andA101. Assuming constancy of evolutionary rate, diversification of the representative alleles of the three humanABOlineages (A101,B101,andO02) was estimated at 4.5 to 6 million years ago.