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

Inactivation of the CMP-N-acetylneuraminic acid hydroxylase gene has provid ed an example of human-specific genomic mutation that results in a widespre ad biochemical difference between human and nonhuman primates. We have foun d that, although a region containing a 92-bp exon and an AluSq element in t he hydroxylase gene is intact in all nonhuman primates examined, the same r egion in the human genome is replaced by an AluY element that was dissemina ted 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 inac tivated the human hydroxylase gene. It is suggested that AN elements have p layed potentially important roles in genotypic and phenotypic evolution in the hominid lineage.