title: Human lineage-specific amplification, selection, and neuronal expression of DUF1220 domains.
abstract: Extreme gene duplication is a major source of evolutionary novelty. A genome-wide survey of gene copy number variation among human and great ape lineages revealed that the most striking human lineage-specific amplification was due to an unknown gene, MGC8902, which is predicted to encode multiple copies of a protein domain of unknown function (DUF1220). Sequences encoding these domains are virtually all primate-specific, show signs of positive selection, and are increasingly amplified generally as a function of a species' evolutionary proximity to humans, where the greatest number of copies (212) is found. DUF1220 domains are highly expressed in brain regions associated with higher cognitive function, and in brain show neuron-specific expression preferentially in cell bodies and dendrites.
authors.affiliation: Human Medical Genetics, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA.
authors.forename: Magdalena C
authors.initials: MC
authors.lastname: Popesco
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Maclaren
authors.forename: Janet
authors.initials: J
authors.lastname: Hopkins
authors.forename: Laura
authors.initials: L
authors.lastname: Dumas
authors.forename: Michael
authors.initials: M
authors.lastname: Cox
authors.forename: Lynne
authors.initials: L
authors.lastname: Meltesen
authors.forename: Loris
authors.initials: L
authors.lastname: McGavran
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Wyckoff
authors.forename: James M
authors.initials: JM
authors.lastname: Sikela
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D001921:Brain / Q000378:metabolism*; D003071:Cognition; D005091:Exons; D005784:Gene Amplification; D018628:Gene Dosage; D020440:Gene Duplication; D015870:Gene Expression; D015894:Genome, Human; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D019579:Neocortex / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D002679:Pan troglodytes / Q000235:genetics; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D051381:Rats; D012641:Selection, Genetic
chemical_list: D011506:Proteins