Evolution of X Chromosome Inactivation and Dosage Compensation

Here I discuss how X chromosome inactivation might have evolved in mammals to compensate for the progressive loss of alleles from the Y chromosome. We can exploit genetic differences between species in the expression and the molecular mechanism of X inactivation to explore how the several layers of silencing could have evolved to build the extraordinarily stable silencing of the inactive X in eutherian mammals. I describe how dosage compensation works (or doesn’t work) in other vertebrates that have differentiated sex chromosomes; monotremes, birds, snakes, even frogs and fish. We must ask the question – how essential is dosage compensation anyway? Are there other ways of coping with dosage inequities brought on by sex chromosome differentiation? I then describe briefly some of the best-known dosage compensation systems, in our invertebrate models, revealing many ancient silencing mechanisms whose components we recognize in fish, flies and humans. These mechanisms are there in all sorts of other systems in which epigenetic silencing has been selected for, constituting an ancient molecular toolbox full of ways to regulate the activities of genes, or of whole regions of the genome.