Dosage compensation

About: Dosage compensation is a research topic. Over the lifetime, 1920 publications have been published within this topic receiving 124589 citations.

A single female-specific piRNA is the primary determiner of sex in the silkworm

Abstract: The silkworm Bombyx mori uses a WZ sex determination system that is analogous to the one found in birds and some reptiles. In this system, males have two Z sex chromosomes, whereas females have Z and W sex chromosomes. The silkworm W chromosome has a dominant role in female determination, suggesting the existence of a dominant feminizing gene in this chromosome. However, the W chromosome is almost fully occupied by transposable element sequences, and no functional protein-coding gene has been identified so far. Female-enriched PIWI-interacting RNAs (piRNAs) are the only known transcripts that are produced from the sex-determining region of the W chromosome, but the function(s) of these piRNAs are unknown. Here we show that a W-chromosome-derived, female-specific piRNA is the feminizing factor of B. mori. This piRNA is produced from a piRNA precursor which we named Fem. Fem sequences were arranged in tandem in the sex-determining region of the W chromosome. Inhibition of Fem-derived piRNA-mediated signalling in female embryos led to the production of the male-specific splice variants of B. mori doublesex (Bmdsx), a gene which acts at the downstream end of the sex differentiation cascade. A target gene of Fem-derived piRNA was identified on the Z chromosome of B. mori. This gene, which we named Masc, encoded a CCCH-type zinc finger protein. We show that the silencing of Masc messenger RNA by Fem piRNA is required for the production of female-specific isoforms of Bmdsx in female embryos, and that Masc protein controls both dosage compensation and masculinization in male embryos. Our study characterizes a single small RNA that is responsible for primary sex determination in the WZ sex determination system.

Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development

Abstract: X-chromosome inactivation (XCI) in female mammals allows dosage compensation for X-linked gene products between the sexes The developmental regulation of this process has been extensively investigated in mice, where the X chromosome of paternal origin (Xp) is silenced during early embryogenesis owing to imprinted expression of the regulatory RNA, Xist (X-inactive specific transcript) Paternal XCI is reversed in the inner cell mass of the blastocyst and random XCI subsequently occurs in epiblast cells Here we show that other eutherian mammals have very different strategies for initiating XCI In rabbits and humans, the Xist homologue is not subject to imprinting and XCI begins later than in mice Furthermore, Xist is upregulated on both X chromosomes in a high proportion of rabbit and human embryo cells, even in the inner cell mass In rabbits, this triggers XCI on both X chromosomes in some cells In humans, chromosome-wide XCI has not initiated even by the blastocyst stage, despite the upregulation of XIST The choice of which X chromosome will finally become inactive thus occurs downstream of Xist upregulation in both rabbits and humans, unlike in mice Our study demonstrates the remarkable diversity in XCI regulation and highlights differences between mammals in their requirement for dosage compensation during early embryogenesis

Model for evolution of Y chromosomes and dosage compensation.

Abstract: Some difficulties with the classical model for the evolution of a genetically invert Y chromosome are discussed. An alternative model is proposed, which is based on the principle of Mullers ratchet; this involves the accumulation of chromosomes bearing deleterious mutant genes in a finite population in the absence of crossing-over. This process would result in the gradual increase, with time, in the number of mutant loci carried in an average Y chromosome, although the frequency of individual deleterious alleles at most loci remains low. It is shown that this creates a selection pressure for differentially increasing the activity of the X chromosome in heterogametic individuals at the expense of that of the Y, leading eventually to a genetically inert Y chromosome and to the evolution of dosage compensation.

The Xist RNA Gene Evolved in Eutherians by Pseudogenization of a Protein-Coding Gene

Abstract: The Xist noncoding RNA is the key initiator of the process of X chromosome inactivation in eutherian mammals, but its precise function and origin remain unknown. Although Xist is well conserved among eutherians, until now, no homolog has been identified in other mammals. We show here that Xist evolved, at least partly, from a protein-coding gene and that the loss of protein-coding function of the proto-Xist coincides with the four flanking protein genes becoming pseudogenes. This event occurred after the divergence between eutherians and marsupials, which suggests that mechanisms of dosage compensation have evolved independently in both lineages.