A proposed path by which genes common to mammalian X and Y chromosomes evolve to become X inactivated.
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.
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02142, USA.
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D000818:Animals; D002460:Cell Line; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D004303:Dosage Compensation, Genetic; D019143:Evolution, Molecular; D005260:Female; D056466:Histone Demethylases; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008297:Male; D008322:Mammals / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D005810:Multigene Family; D010089:Oxidoreductases, N-Demethylating; D011506:Proteins / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics; D014157:Transcription Factors; D014960:X Chromosome; D014998:Y Chromosome
D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D011506:Proteins; D012269:Ribosomal Proteins; D014157:Transcription Factors; C031798:ribosomal protein S4; C062076:zinc finger protein, X-linked; D056466:Histone Demethylases; C086877:KDM5C protein, human; D010089:Oxidoreductases, N-Demethylating