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

Abstract

Mammalian X and Y chromosomes evolved from an autosomal pair; the X retained and the Y gradually lost most ancestral genes. 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 basis. 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, RPS4X and SMCX were monitored for X inactivation in diverse species by assaying CpG-island methylation, which mirrors X inactivation in many eutherians. ZFX 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 RPS4X, escape from X inactivation seems unique to primates. SMCX 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.

Psychiatric epigenetics: a new focus for the new century

“…X-Y homologies are generated by chromosomal re-arrangements and are subject to epigenetic modification that differs across species. 20 These observations are relevant to the hypothesis that the genetic and morphological variations associated with psychosis are echoes of the speciation event in the origin of Homo sapiens, and that this event occurred in a region of X-Y homology that was generated by a translocation that occurred after the separation of the chimpanzee and hominid lineages. 21,22 According to this concept schizophrenia is 'the price that Homo sapiens pays for language', 23 and the variation that gives rise to it reflects the progressive epigenetic modification of the genetic locus that was sexually selected in the transition from a precursor hominid species.…”

X-linked inheritance of Fanconi anemia complementation group B

“…In adult females, most genes on one of the X chromosomes are inactive owing to hypermethylation of their promoter 9 . This X inactivation occurs early in embryogenesis and is randomly determined.…”

Genetic mapping of Z chromosome and identification of W chromosome-specific markers in the silkworm, Bombyx mori

“…Sex chromosomes have evolved independently many times, and Y chromosomes lack genetic recombination over most or all of their length (Jegalian and Page, 1998;Charlesworth and Charlesworth, 2000). In Drosophila melanogaster and humans, the Y chromosome has lost most of its active genes (Carvalho et al, 2001;Lahn et al, 2001), and those remaining appear largely to affect male-specific functions.…”