Dosage compensation

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

Grasshopper genome reveals long-term conservation of the X chromosome and temporal variation in X chromosome evolution

Abstract: Abstract We present the first chromosome-level genome assembly of the grasshopper, Locusta migratoria , one of the largest insect genomes. We use coverage differences between females (XX) and males (X0) to identify the X chromosome gene content and find that the X chromosome shows both complete dosage compensation in somatic tissues and an underrepresentation of testes-expressed genes. Remarkably, X-linked gene content from L. migratoria is highly conserved across four insect orders, namely Orthoptera, Hemiptera, Coleoptera and Diptera, and the 800 Mb grasshopper X chromosome is homologous to the fly ancestral X chromosome despite 400 million years of divergence, suggesting either repeated origin of sex chromosomes with highly similar gene content, or long-term conservation of the X chromosome. We use this broad conservation of the X chromosome to test for temporal dynamics to Fast-X evolution, and find evidence of a recent burst evolution for new X-linked genes in contrast to slow evolution of X-conserved genes. Additionally, our results reveal the X chromosome represents a hotspot for adaptive protein evolution related migration and the locust swarming phenotype. Overall, our results reveal a remarkable case of conservation and adaptation on the X chromosome.

reviews Males, hermaphrodites and females: sex determination in Caenorhabditis elegans

Abstract: TIG- March 1985 Caenorhabditis elegans is a small, free-living nema- tode, about 1 mm long as an adult, which occurs natur'Ally in garden soft. It now, occupies a unique place in development bio- logy because it is the only animal for which a com- plete cell lineage is known, from the single cell of the zygote to the thousand-odd differen- tiated ceils of the adult I-3. It has also become a favourite organism for developmental geneticists, largely as the result of Sydney Brenner's initial worlP. About 500 genes have been mapped and many loci in- volved in controlling development have been studied in detail s . , One aspect of C elegans genetics that has received partimxlar attention is sex determination. Under- standing how a whole animal develops into a male rather than a female is fundamentally the same problem as understanding how one part of an animal develops into an intestine as opposed to a muscle or a leg as opposed to a wing. The analysis of sexual differentiation has a particttlar advantage in that the primary sex-determining signal (for example, the pos- session of a Y chromosome in mammals} can usually be identified. Having defined the first step, it is feasible to work down through subsequent steps, in the hope of identifying the whole chain of events that eventually leads to different sexual phenotypes. In other developmental pathways, the initiating signal (such as a determinant in the egg cytoplasm) is often hypothetical or unknown. Sex determination has been studied in the three animals most favourable for detailed genetic analysis: the mouse, Drosophila and C. elegans (for recent work on the mouse, see Refs 6 and 7; for Drosophila, see Refs 8 and 9). At first sight the mouse and Drosophila, which both have XX females and XY males, seem much more like each other than like the nematode, which has no female sex and no Y chromosome (Table 1). In fact, the two invertebrates are surprisingly similar, and the mouse is the odd one out. In both Drosophila and C. elegans the primary sex- determining signal is not the possession of a particular sex chromosome (as in mammals) but is instead a chromosomal ratio, the ratio of X chromosomes to autosomes. Because the Y chromosome of Drosophila melanogaster has no determinative role (although it carries genes essential for spermatogenesis), and XO genotype in D. melanogaster results in a sterile male phenotype, in contrast to the XO mouse, which is female. Some relatives of D. rnelanogaster, such as/9. annulimana, have no separate Y chromosome and therefore have an XX/XO system like C. elegans. Another property uniting Drosophila and C. elegans is X chromosome dosage compensation. Mammals achieve equal expression of sex-linked genes in the two sexes by X inactivation in the female, so only one X chromosome is active in any given cell. In Drosophila, equal expression is achieved by adjusting X chromosome transcription in male and female so

Paternal easiRNAs regulate parental genome dosage in Arabidopsis

Abstract: The regulation of parental genome dosage is of fundamental importance in animals and plants, exemplified by X chromosome inactivation and dosage compensation. The "triploid block" is a classical example of dosage regulation in plants that establishes a reproductive barrier between species differing in chromosome number. This barrier acts in the endosperm, an ephemeral tissue that nurtures the developing embryo and induces the abortion of hybrid seeds through a yet unknown mechanism. Interploidy hybridizations involving diploid (2x) maternal parents and tetraploid (4x) pollen donors cause failure in endosperm cellularization, leading to embryo arrest. Here we show that paternal epigenetically activated small interfering RNAs (easiRNAs) are responsible for the establishment of the triploid block-associated seed abortion in Arabidopsis thaliana. Paternal loss of the plant-specific RNA polymerase IV suppressed easiRNA formation and rescued triploid seeds by restoring small RNA-directed DNA methylation at transposable elements (TEs), correlating with reduced expression of paternally expressed imprinted genes (PEGs). We propose that excess of paternally derived easiRNAs in diploid pollen prevents establishment of DNA methylation, leading to triploid seed abortion. Our data further suggest that easiRNAs form a quantitative signal for chromosome number and their balanced dosage is required for post-fertilization genome stability and seed viability.

Silencing XIST on the future active X: Searching human and bovine preimplantation embryos for the repressor.

Abstract: X inactivation is the means of equalizing the dosage of X chromosomal genes in male and female eutherian mammals, so that only one X is active in each cell. The XIST locus (in cis) on each additional X chromosome initiates the transcriptional silence of that chromosome, making it an inactive X. How the active X in both males and females is protected from inactivation by its own XIST locus is not well understood in any mammal. Previous studies of autosomal duplications suggest that gene(s) on the short arm of human chromosome 19 repress XIST on the active X. Here, we examine the time of transcription of some candidate genes in preimplantation embryos using single-cell RNA sequencing data from human embryos and qRT-PCR from bovine embryos. The candidate genes assayed are those transcribed from 19p13.3-13.2, which are widely expressed and can remodel chromatin. Our results confirm that XIST is expressed at low levels from the future active X in embryos of both sexes; they also show that the XIST locus is repressed in both sexes when pluripotency factors are being upregulated, during the 4-8 cell and morula stages in human and bovine embryos - well before the early blastocyst (E5) when XIST on the inactive X in females starts to be upregulated. Our data suggest a role for DNMT1, UHRF1, SAFB and SAFB2 in XIST repression; they also exclude XACT and other 19p candidate genes and provide the transcriptional timing for some genes not previously assayed in human or bovine preimplantation embryos.

Dosage Compensation of an Aneuploid Genome in Mouse Spermatogenic Cells

Abstract: Autosomal trisomies and monosomies bring serious threats to embryonic development through transcriptional disarray caused primarily by the dosage effect of the aneuploid part of the genome. The present study compared the effect of a mouse-viable 30-Mb segmental trisomy on the genome-wide transcriptional profile of somatic (liver) cells and male germ cells. Although the 1.6-fold change in expression of triplicated genes reflected the gene dosage in liver cells, the extra copy genes were compensated in early pachytene spermatocytes, showing 1.18-fold increase. Although more pronounced, the dosage compensation of trisomic genes was concordant with the incidence of HORMAD2 protein and histone gammaH2AX markers of unsynapsed chromatin. A possible explanation for this includes insufficient sensitivity to detect the meiotic silencing of unsynapsed chromatin markers in the 30-Mb region of the chromosome or an earlier silencing effect of another epigenetic factor. Taken together, our results indicate that the meiotic silencing of unsynapsed chromatin is the major, but most likely not the only, factor driving the dosage compensation of triplicated genes in primary spermatocytes.