title: The Evolutionary Fates of a Large Segmental Duplication in Mouse.
abstract: Gene duplication and loss are major sources of genetic polymorphism in populations, and are important forces shaping the evolution of genome content and organization. We have reconstructed the origin and history of a 127-kbp segmental duplication, R2d, in the house mouse (Mus musculus). R2d contains a single protein-coding gene, Cwc22 De novo assembly of both the ancestral (R2d1) and the derived (R2d2) copies reveals that they have been subject to nonallelic gene conversion events spanning tens of kilobases. R2d2 is also a hotspot for structural variation: its diploid copy number ranges from zero in the mouse reference genome to >80 in wild mice sampled from around the globe. Hemizygosity for high copy-number alleles of R2d2 is associated in cis with meiotic drive; suppression of meiotic crossovers; and copy-number instability, with a mutation rate in excess of 1 per 100 transmissions in some laboratory populations. Our results provide a striking example of allelic diversity generated by duplication and demonstrate the value of de novo assembly in a phylogenetic context for understanding the mutational processes affecting duplicate genes.
authors.affiliation: Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Andrew P
authors.identifier: http://orcid.org/0000-0003-1942-4543
authors.initials: AP
authors.lastname: Morgan
authors.affiliation: Department of Computer Science, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: J Matthew
authors.initials: JM
authors.lastname: Holt
authors.affiliation: Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Rachel C
authors.initials: RC
authors.lastname: McMullan
authors.affiliation: Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Bell
authors.affiliation: Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Amelia M-F
authors.initials: AM
authors.lastname: Clayshulte
authors.affiliation: Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: John P
authors.initials: JP
authors.lastname: Didion
authors.affiliation: Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Liran
authors.initials: L
authors.lastname: Yadgary
authors.affiliation: European Bioinformatics Institute, European Molecular Biology Laboratory, Wellcome Genome Campus, Cambridge, CB10 1SD, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Thybert
authors.affiliation: Cancer Research United Kingdom Cambridge Institute, University of Cambridge, CB2 0RE, United Kingdom Wellcome Trust Sanger Institute, Wellcome Genome Campus, Cambridge, CB10 1SA, United Kingdom.
authors.forename: Duncan T
authors.initials: DT
authors.lastname: Odom
authors.affiliation: European Bioinformatics Institute, European Molecular Biology Laboratory, Wellcome Genome Campus, Cambridge, CB10 1SD, United Kingdom Wellcome Trust Sanger Institute, Wellcome Genome Campus, Cambridge, CB10 1SA, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Flicek
authors.affiliation: Department of Computer Science, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Leonard
authors.initials: L
authors.lastname: McMillan
authors.affiliation: Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599 fernando@med.unc.edu.
authors.forename: Fernando Pardo-Manuel
authors.initials: FP
authors.lastname: de Villena
mesh_terms: D000483:Alleles; D000818:Animals; D000835:Animals, Wild / Q000235:genetics; D005075:Biological Evolution; D019143:Evolution, Molecular; D005785:Gene Conversion; D018628:Gene Dosage; D020440:Gene Duplication; D020131:Genes, Duplicate; D014644:Genetic Variation; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics*; D010802:Phylogeny; D016601:RNA-Binding Proteins; D056916:Segmental Duplications, Genomic
chemical_list: C000607845:CWC22 protein, mouse; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins
keywords: copy-number variation; meiotic drive; segmental duplications