title: High mutation rates have driven extensive structural polymorphism among human Y chromosomes.
abstract: Although much structural polymorphism in the human genome has been catalogued, the kinetics of underlying change remain largely unexplored. Because human Y chromosomes are clonally inherited, it has been possible to capture their detailed relationships in a robust, worldwide genealogical tree. Examination of structural variation across this tree opens avenues for investigating rates of underlying mutations. We selected one Y chromosome from each of 47 branches of this tree and searched for large-scale variation. Four chromosomal regions showed extensive variation resulting from numerous large-scale mutations. Within the tree encompassed by the studied chromosomes, the distal-Yq heterochromatin changed length > or = 12 times, the TSPY gene array changed length > or = 23 times, the 3.6-Mb IR3/IR3 region changed orientation > or = 12 times and the AZFc region was rearranged > or = 20 times. After determining the total time spanned by all branches of this tree (approximately 1.3 million years or 52,000 generations), we converted these mutation counts to lower bounds on rates: > or = 2.3 x 10(-4), > or = 4.4 x 10(-4), > or = 2.3 x 10(-4) and > or = 3.8 x 10(-4) large-scale mutations per father-to-son Y transmission, respectively. Thus, high mutation rates have driven extensive structural polymorphism among human Y chromosomes. At the same time, we found limited variation in the copy number of Y-linked genes, which raises the possibility of selective constraints.
authors.affiliation: Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Repping
authors.forename: Saskia K M
authors.initials: SK
authors.lastname: van Daalen
authors.forename: Laura G
authors.initials: LG
authors.lastname: Brown
authors.forename: Cindy M
authors.initials: CM
authors.lastname: Korver
authors.forename: Julian
authors.initials: J
authors.lastname: Lange
authors.forename: Janet D
authors.initials: JD
authors.lastname: Marszalek
authors.forename: Tatyana
authors.initials: T
authors.lastname: Pyntikova
authors.forename: Fulco
authors.initials: F
authors.lastname: van der Veen
authors.forename: Helen
authors.initials: H
authors.lastname: Skaletsky
authors.forename: David C
authors.initials: DC
authors.lastname: Page
authors.forename: Steve
authors.initials: S
authors.lastname: Rozen
mesh_terms: D041322:Chromosomes, Human, Y; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic