High mutation rates have driven extensive structural polymorphism among human Y chromosomes.
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.
Repping
Sjoerd
S
Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
van Daalen
Saskia K M
SK
Brown
Laura G
LG
Korver
Cindy M
CM
Lange
Julian
J
Marszalek
Janet D
JD
Pyntikova
Tatyana
T
van der Veen
Fulco
F
Skaletsky
Helen
H
Page
David C
DC
Rozen
Steve
S
D041322:Chromosomes, Human, Y; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic