Dosage compensation

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

Evolution of dosage compensation under sexual selection differs between X and Z chromosomes.

Abstract: Complete sex chromosome dosage compensation has more often been observed in XY than ZW species. In this study, using a population genetic model and the chicken transcriptome, we assess whether sexual conflict can account for this difference. Sexual conflict over expression is inevitable when mutation effects are correlated across the sexes, as compensatory mutations in the heterogametic sex lead to hyperexpression in the homogametic sex. Coupled with stronger selection and greater reproductive variance in males, this results in slower and less complete evolution of Z compared with X dosage compensation. Using expression variance as a measure of selection strength, we find that, as predicted by the model, dosage compensation in the chicken is most pronounced in genes that are under strong selection biased towards females. Our study explains the pattern of weak dosage compensation in ZW systems, and suggests that sexual selection plays a major role in shaping sex chromosome dosage compensation.

Genetic architecture of skewed X inactivation in the laboratory mouse.

Abstract: X chromosome inactivation (XCI) is the mammalian mechanism of dosage compensation that balances X-linked gene expression between the sexes. Early during female development, each cell of the embryo proper independently inactivates one of its two parental X-chromosomes. In mice, the choice of which X chromosome is inactivated is affected by the genotype of a cis-acting locus, the X-chromosome controlling element (Xce). Xce has been localized to a 1.9 Mb interval within the X-inactivation center (Xic), yet its molecular identity and mechanism of action remain unknown. We combined genotype and sequence data for mouse stocks with detailed phenotyping of ten inbred strains and with the development of a statistical model that incorporates phenotyping data from multiple sources to disentangle sources of XCI phenotypic variance in natural female populations on X inactivation. We have reduced the Xce candidate 10-fold to a 176 kb region located approximately 500 kb proximal to Xist. We propose that structural variation in this interval explains the presence of multiple functional Xce alleles in the genus Mus. We have identified a new allele, Xcee present in Mus musculus and a possible sixth functional allele in Mus spicilegus. We have also confirmed a parent-of-origin effect on X inactivation choice and provide evidence that maternal inheritance magnifies the skewing associated with strong Xce alleles. Based on the phylogenetic analysis of 155 laboratory strains and wild mice we conclude that Xcea is either a derived allele that arose concurrently with the domestication of fancy mice but prior the derivation of most classical inbred strains or a rare allele in the wild. Furthermore, we have found that despite the presence of multiple haplotypes in the wild Mus musculus domesticus has only one functional Xce allele, Xceb. Lastly, we conclude that each mouse taxa examined has a different functional Xce allele.

Global impacts of chromosomal imbalance on gene expression in Arabidopsis and other taxa.

Abstract: Changes in dosage of part of the genome (aneuploidy) have long been known to produce much more severe phenotypic consequences than changes in the number of whole genomes (ploidy). To examine the basis of these differences, global gene expression in mature leaf tissue for all five trisomies and in diploids, triploids, and tetraploids of Arabidopsis thaliana was studied. The trisomies displayed a greater spread of expression modulation than the ploidy series. In general, expression of genes on the varied chromosome ranged from compensation to dosage effect, whereas genes from the remainder of the genome ranged from no effect to reduced expression approaching the inverse level of chromosomal imbalance (2/3). Genome-wide DNA methylation was examined in each genotype and found to shift most prominently with trisomy 4 but otherwise exhibited little change, indicating that genetic imbalance is generally mechanistically unrelated to DNA methylation. Independent analysis of gene functional classes demonstrated that ribosomal, proteasomal, and gene body methylated genes were less modulated compared with all classes of genes, whereas transcription factors, signal transduction components, and organelle-targeted protein genes were more tightly inversely affected. Comparing transcription factors and their targets in the trisomies and in expression networks revealed considerable discordance, illustrating that altered regulatory stoichiometry is a major contributor to genetic imbalance. Reanalysis of published data on gene expression in disomic yeast and trisomic mouse cells detected similar stoichiometric effects across broad phylogenetic taxa, and indicated that these effects reflect normal gene regulatory processes.

Expansion of GA Dinucleotide Repeats Increases the Density of CLAMP Binding Sites on the X-Chromosome to Promote Drosophila Dosage Compensation.

Abstract: Dosage compensation is an essential process that equalizes transcript levels of X-linked genes between sexes by forming a domain of coordinated gene expression. Throughout the evolution of Diptera, many different X-chromosomes acquired the ability to be dosage compensated. Once each newly evolved X-chromosome is targeted for dosage compensation in XY males, its active genes are upregulated two-fold to equalize gene expression with XX females. In Drosophila melanogaster, the CLAMP zinc finger protein links the dosage compensation complex to the X-chromosome. However, the mechanism for X-chromosome identification has remained unknown. Here, we combine biochemical, genomic and evolutionary approaches to reveal that expansion of GA-dinucleotide repeats likely accumulated on the X-chromosome over evolutionary time to increase the density of CLAMP binding sites, thereby driving the evolution of dosage compensation. Overall, we present new insight into how subtle changes in genomic architecture, such as expansions of a simple sequence repeat, promote the evolution of coordinated gene expression.

Sex Determination and X Chromosome Dosage Compensation

Abstract: I. INTRODUCTION The choice of sexual fate is an early developmental decision with far reaching consequences. In Caenorhabditis elegans , this decision not only specifies the overt sexual characteristics evident in adults, but also sets the level of X chromosome gene expression in all somatic cells throughout development, starting at the 30-cell stage. The sex determination decision itself must be made with considerable fidelity, despite the fact that only a twofold difference in X chromosome number triggers this major developmental event. Studies during the last two decades have identified many of the genes in the complex regulatory hierarchy that determines sexual fate in C. elegans , stemming from those that comprise the sex-determining signal itself to those that control sexual dimorphism and X chromosome expression. Molecular mechanisms underlying many aspects of sex determination and differentiation have also been revealed. Indeed, studies of sex determination in C. elegans have proven it to be a rich source of information concerning the molecular nature of developmental decisions and how they are regulated. These studies have intersected work in many areas including transcriptional regulation, translational regulation, RNA processing, signal transduction, and chromosome structure. This chapter summarizes our current understanding of the genetic and molecular basis for sex determination and the related process of dosage compensation. The extensive information obtained will facilitate future efforts to tap the enormous potential that this system holds for addressing fundamental biological and biochemical questions. II. SEXUAL DIMORPHISM C. elegans has two natural sexes, XO males and XX hermaphrodites. The hermaphrodites are...