Article

Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators

  • Nature volume 508, pages 494499 (24 April 2014)
  • doi:10.1038/nature13206
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Abstract

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.

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Acknowledgements

We thank W. J. Murphy, E. Owens and J. E. Womak for generating radiation hybrid panels and for assistance in mapping; L. Lyons and W.J.M. for providing the rhesus radiation hybrid panel; A. Kaur for a rhesus cell line; S. Austad, P. Hornsby and S. Tardif for marmoset cell lines; M. Brown for rat cell lines; J.E.W. for bull fibroblasts; W. Johnson and S. O’Neil for rhesus tissues samples; W.J., S.O. and S.T. for marmoset tissue samples; M. Turner for rat tissue samples; J.E.W. for bull tissue samples; P. Samollow for opossum tissue samples; E. Vallender for Tamarin DNA; B. Chowdhary and T. Raudsepp for FISH experiments in the bull; C. Friedman and B. Trask for flow-sorted marmoset Y chromosomes; B.T. for sizing rat Y chromosomes; C. Burge for permission to assemble transcriptome data from SRR594455, SRR594463 and SRR594508; J. Alföldi for permission to assemble transcriptome data from SRR500909; R.B. Norgren for permission to assemble transcriptome data from SRR544870; and A. Godfrey, Y. Hu and B. Lesch for comments on the manuscript. Supported by National Institutes of Health and Howard Hughes Medical Institute.

Author information

Affiliations

  1. Whitehead Institute, Howard Hughes Medical Institute, & Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA

    • Daniel W. Bellott
    • , Jennifer F. Hughes
    • , Helen Skaletsky
    • , Laura G. Brown
    • , Tatyana Pyntikova
    • , Ting-Jan Cho
    • , Natalia Koutseva
    • , Sara Zaghlul
    • , Jessica Alföldi
    • , Steve Rozen
    •  & David C. Page
  2. The Genome Institute, Washington University School of Medicine, St. Louis, Missouri 63108, USA

    • Tina Graves
    • , Susie Rock
    • , Colin Kremitzki
    • , Robert S. Fulton
    • , Wesley C. Warren
    •  & Richard K. Wilson
  3. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA

    • Shannon Dugan
    • , Yan Ding
    • , Donna Morton
    • , Ziad Khan
    • , Lora Lewis
    • , Christian Buhay
    • , Qiaoyan Wang
    • , Jennifer Watt
    • , Michael Holder
    • , Sandy Lee
    • , Lynne Nazareth
    • , Donna M. Muzny
    •  & Richard A. Gibbs

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Contributions

D.W.B., J.F.H., H.S., S. Rozen, W.C.W., R.A.G., R.K.W. and D.C.P. planned the project. J.F.H., H.S., L.G.B., T.-J.C., N.K., S.Z. and J.A. performed BAC mapping, radiation hybrid mapping and real-time polymerase chain reaction analyses. T.G., S. Rock, C.K., R.S.F., S.D., Y.D., D.M., Z.K., L.L., C.B., Q.W., J.W., M.H., S.L., L.N. and D.M.M. were responsible for BAC sequencing. D.W.B., J.F.H. and H.S. performed comparative sequence analyses. T.P. performed FISH analyses. D.W.B. and D.C.P. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Daniel W. Bellott.

Extended data

Supplementary information

Text files

  1. 1.

    Supplementary Data 1

    This data file contains FASTA alignment of X-Y pairs with GGA ORFs.

  2. 2.

    Supplementary Data 2

    This data file contains FASTA sequences used to generate alignments.

Excel files

  1. 1.

    Supplementary Tables

    This file contains Supplementary Tables 1-5.

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