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A proposed path by which genes common to mammalian X and Y chromosomes evolve to become X inactivated

Nature volume 394, pages 776–780 (1998)Cite this article

Abstract

Mammalian X and Y chromosomes evolved from an autosomal pair; the X retained and the Y gradually lost most ancestral genes1,2. In females, one X chromosome is silenced by X inactivation, a process that is often assumed to have evolved on a broadly regional or chromosomal basis3. Here we propose that genes or clusters common to both the X and Y chromosomes (X–Y genes) evolved independently along a multistep path, eventually acquiring dosage compensation on the X chromosome. Three genes studied here, and other extant genes, appear to be intermediates. ZFX, RPS4 and SMC were monitored for X inactivation in diverse species by assaying CpG-island methylation, which mirrors X inactivation in many eutherians. ZF evidently escaped X inactivation in proto-eutherians, which also possessed a very similar Y-linked gene; both characteristics were retained in most extant orders, but not in myomorph rodents. For RPS4, escape from X inactivation seems unique to primates. SMC escapes inactivation in primates and myomorphs but not in several other lineages. Thus, X inactivation can evolve independently for each of these genes. We propose that it is an adaptation to the decay of a homologous, Y-linked gene.

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Figure 1: CpG-island methylation studies of four genes in five eutherian species.
Figure 2: Summary of studies of CpG-island methylation and Y-chromosome homologue in 26 mammalian species, arranged phylogenetically28
Figure 3: Southern blotting reveals closely related, Y-chromosomal homologue of ZF in many eutherians, but not myomorph rodents.
Figure 4: A proposed pathway for X–Y gene evolution in mammals.

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Acknowledgements

We thank the New England Aquarium, the San Diego Zoo, the Duke Primate Center, K. Fredga and K. Campbell for help in obtaining animal specimens; A. Agulnik for a mouse Smc cDNA clone; D. Graur and B. Lahn for helpful discussions; J. Graves for permission to cite unpublished work; J.Cook-Chrysos for graphic art; and D. Bartel, B. Charlesworth, A. Chess, C. Disteche, G. Fink, J. Graves, R. Jaenisch, T. Kawaguchi, M. L. Pardue, D. Schlessinger, C. Sun, H. Willard and A. Zinn for comments on the manuscript. This work was supported by the National Institutes of Health and the Howard Hughes Medical Institute.

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  1. Howard Hughes Medical Institute, Whitehead Institute,

    Karin Jegalian & David C. Page

  2. Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, 02142, Massachusetts, USA

    Karin Jegalian & David C. Page

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  1. Karin Jegalian
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Correspondence to David C. Page.

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Jegalian, K., Page, D. A proposed path by which genes common to mammalian X and Y chromosomes evolve to become X inactivated. Nature 394, 776–780 (1998). https://doi.org/10.1038/29522

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