Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection.
Many human Y-chromosomal deletions are thought to severely impair reproductive fitness, which precludes their transmission to the next generation and thus ensures their rarity in the population. Here we report a 1.6-Mb deletion that persists over generations and is sufficiently common to be considered a polymorphism. We hypothesized that this deletion might affect spermatogenesis because it removes almost half of the Y chromosome's AZFc region, a gene-rich segment that is critical for sperm production. An association study established that this deletion, called gr/gr, is a significant risk factor for spermatogenic failure. The gr/gr deletion has far lower penetrance with respect to spermatogenic failure than previously characterized Y-chromosomal deletions; it is often transmitted from father to son. By studying the distribution of gr/gr-deleted chromosomes across the branches of the Y chromosome's genealogical tree, we determined that this deletion arose independently at least 14 times in human history. We suggest that the existence of this deletion as a polymorphism reflects a balance between haploid selection, which culls gr/gr-deleted Y chromosomes from the population, and homologous recombination, which continues to generate new gr/gr deletions.
Repping
Sjoerd
S
Howard Hughes Medical Institute, Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Skaletsky
Helen
H
Brown
Laura
L
van Daalen
Saskia K M
SK
Korver
Cindy M
CM
Pyntikova
Tatyana
T
Kuroda-Kawaguchi
Tomoko
T
de Vries
Jan W A
JW
Oates
Robert D
RD
Silber
Sherman
S
van der Veen
Fulco
F
Page
David C
DC
Rozen
Steve
S
D002872:Chromosome Deletion; D041322:Chromosomes, Human, Y; D006238:Haploidy; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic