title: Ancestral reconstruction of segmental duplications reveals punctuated cores of human genome evolution.
abstract: Human segmental duplications are hotspots for nonallelic homologous recombination leading to genomic disorders, copy-number polymorphisms and gene and transcript innovations. The complex structure and history of these regions have precluded a global evolutionary analysis. Combining a modified A-Bruijn graph algorithm with comparative genome sequence data, we identify the origin of 4,692 ancestral duplication loci and use these to cluster 437 complex duplication blocks into 24 distinct groups. The sequence-divergence data between ancestral-derivative pairs and a comparison with the chimpanzee and macaque genome support a 'punctuated' model of evolution. Our analysis reveals that human segmental duplications are frequently organized around 'core' duplicons, which are enriched for transcripts and, in some cases, encode primate-specific genes undergoing positive selection. We hypothesize that the rapid expansion and fixation of some intrachromosomal segmental duplications during great-ape evolution has been due to the selective advantage conferred by these genes and transcripts embedded within these core duplications.
authors.affiliation: Department of Genome Sciences, University of Washington School of Medicine and the Howard Hughes Medical Institute, 1705 NE Pacific Street, Seattle, Washington 98195, USA.
authors.forename: Zhaoshi
authors.initials: Z
authors.lastname: Jiang
authors.forename: Haixu
authors.initials: H
authors.lastname: Tang
authors.forename: Mario
authors.initials: M
authors.lastname: Ventura
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Cardone
authors.forename: Tomas
authors.initials: T
authors.lastname: Marques-Bonet
authors.forename: Xinwei
authors.initials: X
authors.lastname: She
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Pevzner
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
mesh_terms: D000818:Animals; D002877:Chromosomes, Human / Q000235:genetics*; D003198:Computer Simulation; D019143:Evolution, Molecular; D018628:Gene Dosage; D020440:Gene Duplication; D008040:Genetic Linkage; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008957:Models, Genetic; D002679:Pan troglodytes / Q000235:genetics; D010802:Phylogeny; D012641:Selection, Genetic