Dosage compensation

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

Translational compensation of gene copy number alterations by aneuploidy in Drosophila melanogaster

Abstract: Chromosomal or segmental aneuploidy-the gain or loss of whole or partial chromosomes-is typically deleterious for organisms, a hallmark of cancers, and only occasionally adaptive. To understand the cellular and organismal consequences of aneuploidy, it is important to determine how altered gene doses impact gene expression. Previous studies show that, for some Drosophila cell lines but not others, the dose effect of segmental aneuploidy can be moderately compensated at the mRNA level - aneuploid gene expression is shifted towards wild-type levels. Here, by analyzing genome-wide translation efficiency estimated with ribosome footprint data from the aneuploid Drosophila S2 cell line, we report that the dose effect of aneuploidy can be further compensated at the translational level. Intriguingly, we find no comparable translational compensation in the aneuploid Kc167 cell line. Comparing the properties of aneuploid genes from the two cell lines suggests that selective constraint on gene expression, but neither sequence features nor functions, may partly explain why the two cell lines differ in translational compensation. Our results, together with previous observations that compensation at the mRNA level also varies among Drosophila cell lines and yeast strains, suggest that dosage compensation of aneuploidy is not general but contingent on genotypic and/or developmental context.

DNA Sequence Homology between the Human Sex Chromosomes

Abstract: Publisher Summary The genetic functions carried by the sex chromosomes have become the subject of investigation because of the opportunity afforded by the functional monosomy of the X and Y chromosomes in males. The view of the mammalian sex chromosomes perceives their evolution from an ancestral pair of homologs. Morphological differentiation has accompanied the emergence of a sex-determining role on the Y and a mechanism of dosage compensation for X-linked genes in females, mediated by random X inactivation. It might be expected that sequence homology from ancestral times might have been retained in functionally important domains of the sex chromosomes. Despite their disparity in size and morphology, the X and Y chromosomes pair at meiosis, ensuring correct segregation during gametogenesis. The failure of the sex chromosomes to participate in recombination beyond the pairing region has precluded a conventional genetic analysis for most of the Y. Suppression of recombination is likely to be an essential requirement for preserving the sex-determining role of the differential part of the Y. Models of the Y have relied on phenotype-karyotype correlations through detailed cytogenetic analysis of abnormal Y chromosomes. Models of the Y derived from such studies reflect the level of resolution that cytogenetics can provide.

Do male and female heterogamety really differ in expression regulation? Lack of global dosage balance in pygopodid geckos.

Abstract: Differentiation of sex chromosomes is thought to have evolved with cessation of recombination and subsequent loss of genes from the degenerated partner (Y and W) of sex chromosomes, which in turn leads to imbalance of gene dosage between sexes. Based on work with traditional model species, theory suggests that unequal gene copy numbers lead to the evolution of mechanisms to counter this imbalance. Dosage compensation, or at least achieving dosage balance in expression of sex-linked genes between sexes, has largely been documented in lineages with male heterogamety (XX/XY sex determination), while ZZ/ZW systems are assumed to be usually associated with the lack of chromosome-wide gene dose regulatory mechanisms. Here, we document that although the pygopodid geckos evolved male heterogamety with a degenerated Y chromosome 32-72 Ma, one species in particular, Burton's legless lizard (Lialis burtonis), does not possess dosage balance in the expression of genes in its X-specific region. We summarize studies on gene dose regulatory mechanisms in animals and conclude that there is in them no significant dichotomy between male and female heterogamety. We speculate that gene dose regulatory mechanisms are likely to be related to the general mechanisms of sex determination instead of type of heterogamety. This article is part of the theme issue 'Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)'.

Single-Cell Analysis Reveals Partial Reactivation of X Chromosome instead of Chromosome-wide Dampening in Naive Human Pluripotent Stem Cells

Abstract: Recently, a unique form of X chromosome dosage compensation has been demonstrated in human preimplantation embryos, which happens through the dampening of X-linked gene expression from both X chromosomes. Subsequently, X chromosome dampening has also been demonstrated in female human pluripotent stem cells (hPSCs) during the transition from primed to naive state. However, the existence of dampened X chromosomes in both embryos and hPSCs remains controversial. Specifically, in preimplantation embryos it has been shown that there is inactivation of X chromosome instead of dampening. Here, we performed allelic analysis of X-linked genes at the single-cell level in hPSCs and found that there is partial reactivation of the inactive X chromosome instead of chromosome-wide dampening upon conversion from primed to naive state. In addition, our analysis suggests that the reduced X-linked gene expression in naive hPSCs might be the consequence of erasure of active X chromosome upregulation.