Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators.
The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three per cent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes. Our findings indicate that survival was nonrandom, and in two cases, convergent across placental and marsupial mammals. We conclude that the gene content of the Y chromosome became specialized through selection to maintain the ancestral dosage of homologous X-Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability. We propose that beyond its roles in testis determination and spermatogenesis, the Y chromosome is essential for male viability, and has unappreciated roles in Turner's syndrome and in phenotypic differences between the sexes in health and disease.
Whitehead Institute, Howard Hughes Medical Institute, & Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Daniel W
DW
Bellott
Whitehead Institute, Howard Hughes Medical Institute, & Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Jennifer F
JF
Hughes
Whitehead Institute, Howard Hughes Medical Institute, & Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Helen
H
Skaletsky
Whitehead Institute, Howard Hughes Medical Institute, & Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Laura G
LG
Brown
Whitehead Institute, Howard Hughes Medical Institute, & Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Tatyana
T
Pyntikova
Whitehead Institute, Howard Hughes Medical Institute, & Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Ting-Jan
TJ
Cho
Whitehead Institute, Howard Hughes Medical Institute, & Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Natalia
N
Koutseva
Whitehead Institute, Howard Hughes Medical Institute, & Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Sara
S
Zaghlul
The Genome Institute, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Tina
T
Graves
The Genome Institute, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Susie
S
Rock
The Genome Institute, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Colin
C
Kremitzki
The Genome Institute, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Robert S
RS
Fulton
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Shannon
S
Dugan
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Yan
Y
Ding
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Donna
D
Morton
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Ziad
Z
Khan
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Lora
L
Lewis
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Christian
C
Buhay
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Qiaoyan
Q
Wang
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Jennifer
J
Watt
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Michael
M
Holder
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Sandy
S
Lee
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Lynne
L
Nazareth
Whitehead Institute, Howard Hughes Medical Institute, & Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Jessica
J
Alföldi
Whitehead Institute, Howard Hughes Medical Institute, & Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Steve
S
Rozen
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Donna M
DM
Muzny
The Genome Institute, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Wesley C
WC
Warren
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Richard A
RA
Gibbs
The Genome Institute, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Richard K
RK
Wilson
Whitehead Institute, Howard Hughes Medical Institute, & Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
David C
DC
Page
D000818:Animals; D041321:Chromosomes, Human, X / Q000235:genetics; D041322:Chromosomes, Human, Y / Q000235:genetics; D004194:Disease; D019143:Evolution, Molecular; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D005786:Gene Expression Regulation; D006262:Health; D006801:Humans; D008297:Male; D008322:Mammals / Q000235:genetics*; D008394:Marsupialia / Q000235:genetics; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis / Q000235:genetics; D055550:Protein Stability; D012641:Selection, Genetic / Q000235:genetics; D017385:Sequence Homology; D012727:Sex Characteristics; D013091:Spermatogenesis / Q000235:genetics; D013737:Testis / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014424:Turner Syndrome / Q000235:genetics; D014960:X Chromosome / Q000235:genetics; D014998:Y Chromosome / Q000235:genetics*