Alu-mediated inactivation of the human CMP-N-acetylneuraminic acid hydroxylase gene

Inactivation of the CMP-N-acetylneuraminic acid hydroxylase gene has provided an example of human-specific genomic mutation that results in a widespread biochemical difference between human and nonhuman primates. We have found that, although a region containing a 92-bp exon and an AluSq element in the hydroxylase gene is intact in all nonhuman primates examined, the same region in the human genome is replaced by an AluY element that was disseminated at least one million years ago. We propose a mechanistic model for this Alu-mediated replacement event, which deleted the 92-bp exon and thus inactivated the human hydroxylase gene. It is suggested that AN elements have played potentially important roles in genotypic and phenotypic evolution in the hominid lineage.