TY - JOUR
T1 - High mutation rates have driven extensive structural polymorphism among human Y chromosomes
AU - Repping, Sjoerd
AU - Van Daalen, Saskia K.M.
AU - Brown, Laura G.
AU - Korver, Cindy M.
AU - Lange, Julian
AU - Marszalek, Janet D.
AU - Pyntikova, Tatyana
AU - Van Der Veen, Fulco
AU - Skaletsky, Helen
AU - Page, David C.
AU - Rozen, Steve
PY - 2006/4
Y1 - 2006/4
N2 - Although much structural polymorphism in the human genome has been catalogued1-5, 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 tree6,7. 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 ≥12 times, the TSPY gene array changed length ≥23 times, the 3.6-Mb IR3/IR3 region changed orientation ≥12 times and the AZFc region was rearranged ≥20 times. After determining the total time spanned by all branches of this tree (∼1.3 million years or 52,000 generations), we converted these mutation counts to lower bounds on rates: ≥2.3 × 10-4, ≥4.4 × 10-4, ≥2.3 × 10-4 and >3.8 × 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.
AB - Although much structural polymorphism in the human genome has been catalogued1-5, 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 tree6,7. 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 ≥12 times, the TSPY gene array changed length ≥23 times, the 3.6-Mb IR3/IR3 region changed orientation ≥12 times and the AZFc region was rearranged ≥20 times. After determining the total time spanned by all branches of this tree (∼1.3 million years or 52,000 generations), we converted these mutation counts to lower bounds on rates: ≥2.3 × 10-4, ≥4.4 × 10-4, ≥2.3 × 10-4 and >3.8 × 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.
UR - https://www.scopus.com/pages/publications/33645418499
U2 - 10.1038/ng1754
DO - 10.1038/ng1754
M3 - 文章
C2 - 16501575
AN - SCOPUS:33645418499
SN - 1061-4036
VL - 38
SP - 463
EP - 467
JO - Nature Genetics
JF - Nature Genetics
IS - 4
ER -