Dosage compensation

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

Temporal genomic evolution of bird sex chromosomes

Abstract: Sex chromosomes exhibit many unusual patterns in sequence and gene expression relative to autosomes. Birds have evolved a female heterogametic sex system (male ZZ, female ZW), through stepwise suppression of recombination between chrZ and chrW. To address the broad patterns and complex driving forces of Z chromosome evolution, we analyze here 45 newly available bird genomes and four species’ transcriptomes, over their course of recombination loss between the sex chromosomes. We show Z chromosomes in general have a significantly higher substitution rate in introns and synonymous protein-coding sites than autosomes, driven by the male-to-female mutation bias (‘male-driven evolution’ effect). Our genome-wide estimate reveals that the degree of such a bias ranges from 1.6 to 3.8 among different species. G + C content of third codon positions exhibits the same trend of gradual changes with that of introns, between chrZ and autosomes or regions with increasing ages of becoming Z-linked, therefore codon usage bias in birds is probably driven by the mutational bias. On the other hand, Z chromosomes also evolve significantly faster at nonsynonymous sites relative to autosomes (‘fast-Z’ evolution). And species with a lower level of intronic heterozygosities tend to evolve even faster on the Z chromosome. Further analysis of fast-evolving genes’ enriched functional categories and sex-biased expression patterns support that, fast-Z evolution in birds is mainly driven by genetic drift. Finally, we show in species except for chicken, gene expression becomes more male-biased within Z-linked regions that have became hemizygous in females for a longer time, suggesting a lack of global dosage compensation in birds, and the reported regional dosage compensation in chicken has only evolved very recently. In conclusion, we uncover that the sequence and expression patterns of Z chromosome genes covary with their ages of becoming Z-linked. In contrast to the mammalian X chromosomes, such patterns are mainly driven by mutational bias and genetic drift in birds, due to the opposite sex-biased inheritance of Z vs. X.

Gene Balance Predicts Transcriptional Responses Immediately Following Ploidy Change in Arabidopsis thaliana.

Abstract: The gene balance hypothesis postulates that there is selection on gene copy number (gene dosage) to preserve the stoichiometric balance among interacting proteins. This presupposes that gene product abundance is governed by gene dosage and that gene dosage responses are consistent for interacting genes in a dosage-balance-sensitive network or complex. Gene dosage responses, however, have rarely been quantified, and the available data suggest that they are highly variable. We sequenced the transcriptomes of two synthetic autopolyploid accessions of Arabidopsis (Arabidopsis thaliana) and their diploid progenitors, as well as one natural tetraploid and its synthetic diploid produced via haploid induction, to estimate transcriptome size and dosage responses immediately following ploidy change. Similar to what has been observed in previous studies, overall transcriptome size does not exhibit a simple doubling in response to genome doubling, and individual gene dosage responses are highly variable in all three accessions, indicating that expression is not strictly coupled with gene dosage. Nonetheless, putatively dosage balance-sensitive gene groups (Gene Ontology terms, metabolic networks, gene families, and predicted interacting proteins) exhibit smaller and more coordinated dosage responses than do putatively dosage-insensitive gene groups, suggesting that constraints on dosage balance operate immediately following whole-genome duplication and that duplicate gene retention patterns are shaped by selection to preserve dosage balance.

Female human primordial germ cells display X-chromosome dosage compensation despite the absence of X-inactivation

Abstract: X-chromosome dosage compensation in female placental mammals is achieved by X-chromosome inactivation (XCI). Human pre-implantation embryos are an exception, in which dosage compensation occurs by X-chromosome dampening (XCD). Here, we examined whether XCD extends to human prenatal germ cells given their similarities to naive pluripotent cells. We found that female human primordial germ cells (hPGCs) display reduced X-linked gene expression before entering meiosis. Moreover, in hPGCs, both X chromosomes are active and express the long non-coding RNAs X active coating transcript (XACT) and X inactive specific transcript (XIST)-the master regulator of XCI-which are silenced after entry into meiosis. We find that XACT is a hPGC marker, describe XCD associated with XIST expression in hPGCs and suggest that XCD evolved in humans to regulate X-linked genes in pre-implantation embryos and PGCs. Furthermore, we found a unique mechanism of X-chromosome regulation in human primordial oocytes. Therefore, future studies of human germline development must consider the sexually dimorphic X-chromosome dosage compensation mechanisms in the prenatal germline.