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The human CMP-N-acetylneuraminic acid hydroxylase gene (CMAH) suffered deletion of an exon that encodes an active center for the enzyme approximately 3.2 million years ago (MYA). We analyzed a 7.3-kb intronic region of 132 CMAH genes to explore the fixation process of this pseudogene and the demographic implication of its haplotype diversity. Fifty-six variable sites were sorted into 18 different haplotypes with significant linkage disequilibrium. Despite the rather low nucleotide diversity, the most recent common ancestor at CMAH dates to 2.9 MYA. This deep genealogy follows shortly after the original exon deletion, indicating that the deletion has fixed in the population, although whether this fixation was facilitated by natural selection remains to be resolved. Remarkable features are exceptionally long persistence of two lineages and the confinement of one lineage in Africa, implying that some African local populations were in relative isolation while others were directly involved in multiple African exoduses of the genus Homo. Importantly, haplotypes found in Eurasia suggest interbreeding between then-contemporaneous human species. Although population structure within Africa complicates the interpretation of phylogeographic information of haplotypes, the data support a single origin of modern humans, but not with complete replacement of archaic inhabitants by modern humans.

Fixation of the Human-Specific CMP-N-Acetylneuraminic Acid Hydroxylase Pseudogene and Implications of Haplotype Diversity for Human Evolution