Abstract
X chromosome inactivation in eutherian mammals has been thought to be tightly controlled, as expected from a mechanism that compensates for the different dosage of X-borne genes in XX females and XY males. However, many X genes escape inactivation in humans, inactivation of the X in marsupials is partial, and the unrelated sex chromosomes of monotreme mammals have incomplete and gene-specific inactivation of X-linked genes. The bird ZW sex chromosome system represents a third independently evolved amniote sex chromosome system with dosage compensation, albeit partial and gene-specific, via an unknown mechanism (i.e. upregulation of the single Z in females, down regulation of one or both Zs in males, or a combination). We used RNA-fluorescent in situ hybridization (RNA-FISH) to demonstrate, on individual fibroblast cells, inactivation of 11 genes on the chicken Z and 28 genes on the X chromosomes of platypus. Each gene displayed a reproducible frequency of 1Z/1X-active and 2Z/2X-active cells in the homogametic sex. Our results indicate that the probability of inactivation is controlled on a gene-by-gene basis (or small domains) on the chicken Z and platypus X chromosomes. This regulatory mechanism must have been exapted independently to the non-homologous sex chromosomes in birds and mammals in response to an over-expressed Z or X in the homogametic sex, highlighting the universal importance that (at least partial) silencing plays in the evolution on amniote dosage compensation and, therefore, the differentiation of sex chromosomes.
Highlights
Vertebrates with heteromorphic sex chromosomes have either male heterogamety like humans (XX female and XY male), or female heterogamety like birds (ZZ male and ZW female)
Dosage compensation is a mechanism that restores the expression of X chromosome genes back to their original level when Y homologues lose function
Our results suggest that the silencing of genes on sex chromosomes has evolved independently in birds and mammals, and is, a critical step in the pathway to dosage compensate independently evolved amniote sex chromosomes systems
Summary
Vertebrates with heteromorphic sex chromosomes have either male heterogamety like humans (XX female and XY male), or female heterogamety like birds (ZZ male and ZW female). Degeneration of the non-recombining Y or W chromosome, central to the evolution of sex chromosomes, left genes on the X or Z as a single copy in the heterogametic sex. This resulted in an imbalance of X or Z gene dosage relative to the autosomes, and between the sexes. Ohno [1] hypothesized that degeneration of the Y/W chromosome would result in under expression from the X/Z in the heterogametic sex (equivalent to monosomy), which would result in pressure to up regulate the single X/Z to restore parity with the autosomes. Recent data has questioned global over regulation of the X/Z [3,4], sparking considerable debate [5,6,7] and suggestion that dosage compensation evolved in response to a subset of dosage sensitive genes [8]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call