Genetic basis for the lack of N-glycolylneuraminic acid expression in human tissues and its implication to human evolution

Sialic acid is a family of acidic monosaccharides and consists of over 30 derivatives. Two major derivatives are N-acetylneuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuGc), and the hydroxylation of CMP-NeuAc is the rate limiting reaction for the production of NeuGc. The hydroxylation was carried out by a complex formed with hydroxylase, cytochrome b5, and NADH-cytochrome b5 reductase. Mouse hydroxylase was purified from the cytosolic fraction of the liver and its cDNA was cloned. Normal human tissues do not contain NeuGc. Human hydroxylase cDNA was also cloned and the sequence revealed that human hydroxylase has 92 bp deletion. The deletion is the cause of defective expression of NeuGc in human. Chimpanzee has intact hydroxylase gene and the 92 bp deletion occurred after the divergence of human ancestor from chimpanzee ancestor. Biochemical and molecular biological studies on the biosynthesis of NeuGc and biological functions of NeuGc are reviewed.