title: Inactivation of MOXD2 and S100A15A by exon deletion during human evolution.
abstract: We devised a bioinformatics method for systematic identification of putative human-specific exon-deletion mutations that occurred after the divergence of human and chimpanzee and experimentally verified 2 of the predicted mutations in MOXD2 and S100A15A genes. MOXD2 gene encodes a monooxygenase that is highly conserved in mammals and is mostly expressed in the olfactory epithelium in mouse. The presence of a deletion of the last 2 exons and a polymorphic nonsense mutation in exon 6 suggests that MOXD2 gene is inactive in humans. S100A15A is a member of the S100 family of calcium-binding proteins, the mouse ortholog of which is expressed during epidermal maturation. Human S100A15A gene is likely to be inactive because the start codon-bearing exon is deleted in human. We propose that modification or inactivation of MOXD2 and S100A15A genes have contributed to the loss of certain smell sense in humans and to the development of human skin.
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Yoonsoo
authors.initials: Y
authors.lastname: Hahn
authors.forename: Sangkyun
authors.initials: S
authors.lastname: Jeong
authors.forename: Byungkook
authors.initials: B
authors.lastname: Lee
mesh_terms: D000818:Animals; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods*; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D006071:Gorilla gorilla / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D006899:Mixed Function Oxygenases / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009831:Olfactory Mucosa / Q000201:enzymology; D002679:Pan troglodytes / Q000235:genetics; D010802:Phylogeny; D011148:Pongo pygmaeus / Q000235:genetics; D009418:S100 Proteins / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D012879:Skin Physiological Phenomena
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D009418:S100 Proteins; D006899:Mixed Function Oxygenases; C114881:MOXD1 protein, human; C527995:MOXD2P protein, human