RT Journal Article SR Electronic T1 Preexisting heterogeneities in gene dosage sensitivity shaped sex chromosome evolution in mammals and birds JF bioRxiv FD Cold Spring Harbor Laboratory SP 119016 DO 10.1101/119016 A1 Sahin Naqvi A1 Daniel W. Bellott A1 David C. Page YR 2017 UL http://biorxiv.org/content/early/2017/03/21/119016.abstract AB Mammalian X and Y chromosomes evolved from an ordinary autosomal pair; genetic decay decimated the Y, which in turn necessitated X chromosome inactivation (XCI). Genes of the ancestral autosomes are often assumed to have undertaken these transitions on uniform terms, but we hypothesized that they varied in their dosage constraints. We inferred such constraints from conservation of microRNA (miRNA)-mediated repression, validated by analysis of experimental data. X-linked genes with a surviving Y homolog have the most conserved miRNA target sites, followed by genes with no Y homolog and subject to XCI, and then genes with no Y homolog but escaping XCI; this heterogeneity existed on the ancestral autosomes. Similar results for avian Z-linked genes, with or without a W homolog, lead to a model of XY/ZW evolution incorporating preexisting dosage sensitivities of individual genes in determining their evolutionary fates, and ultimately shaping the mammalian and avian sex chromosomes.