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The epigenetic sole of sex and dosage compensation

Nature Genetics volume 46, pages 215–217 (2014)Cite this article

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Sex chromosomes in mammals, birds, reptiles and fish represent many independent evolutionary events, but there is spectacular convergence and stunning parallels. A new study details the early stages of ZW differentiation and sex determination in a flatfish and the establishment of dosage compensation and sex reversal by epigenetic mechanisms including DNA methylation.

Sex chromosomes are nothing but trouble. Once an autosome pair acquires a sex-determining gene, degradation of a sex-specific Y or W chromosome sets in, leading to pairing difficulties, the 'peril of hemizygosity' and unequal gene dosage between the sexes. Our understanding of how sex chromosomes evolve and how gene expression is modified to mitigate the consequent problems comes mostly from studies of the mammalian XY and bird ZW sex-chromosome pairs, but both systems evolved hundreds of millions of years ago, so the trail has gone rather cold. On page 253 of this issue, Songlin Chen and colleagues1 report sequencing of the Chinese half-smooth tongue sole, Cynoglossus semilaevis. The decision to study this flatfish species is appropriate, as this fish is rather flexible about sex. It boasts 30 million–year-old Z and Y sex chromosomes (ZZ in males and ZW in females, as in birds) but also has a mechanism for sex reversal, with a high-temperature override that produces fertile ZW pseudomales. This separates sex determination from sex chromosomes, permitting identification of the genes and modifications that determine sex and dosage.

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Figure 1: Regulation of sex determination in the tongue sole.

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  1. Jennifer A. Marshall Graves is at the La Trobe Institute of Molecular Science, Melbourne, Victoria, Australia.,

    Jennifer A Marshall Graves

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  1. Jennifer A Marshall Graves
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Correspondence to Jennifer A Marshall Graves.

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Graves, J. The epigenetic sole of sex and dosage compensation. Nat Genet 46, 215–217 (2014). https://doi.org/10.1038/ng.2903

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