Mechanisms and Evolutionary Patterns of Mammalian and Avian Dosage Compensation

Julien, Philippe; Brawand, David; Soumillon, Magali; Necşulea, Anamaria; Liechti, Angélica; Schütz, Frédéric; Daish, Tasman; Grützner, Frank; Kaessmann, Henrik

doi:10.1371/journal.pbio.1001328

Cited by 211 publications

(338 citation statements)

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“…To test Ohno's hypothesis more directly, attempts have been made to define those genes present on the autosomal progenitor of the X chromosome using species from major mammalian and bird lineages (Julien et al 2012;Lin et al 2012). If the X chromosome is upregulated, transcriptional output from the present-day X and its autosomal progenitor should be similar.…”

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Sex-Biased Gene Expression and Evolution of the X Chromosome in Nematodes

et al. 2014

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Studies of X chromosome evolution in various organisms have indicated that sex-biased genes are nonrandomly distributed between the X and autosomes. Here, to extend these studies to nematodes, we annotated and analyzed X chromosome gene content in four Caenorhabditis species and in Pristionchus pacificus. Our gene expression analyses comparing young adult male and female mRNAseq data indicate that, in general, nematode X chromosomes are enriched for genes with high female-biased expression and depleted of genes with high male-biased expression. Genes with low sex-biased expression do not show the same trend of X chromosome enrichment and depletion. Combined with the observation that highly sex-biased genes are primarily expressed in the gonad, differential distribution of sex-biased genes reflects differences in evolutionary pressures linked to tissue-specific regulation of X chromosome transcription. Our data also indicate that X dosage imbalance between males (XO) and females (XX) is influential in shaping both expression and gene content of the X chromosome. Predicted upregulation of the single male X to match autosomal transcription (Ohno's hypothesis) is supported by our observation that overall transcript levels from the X and autosomes are similar for highly expressed genes. However, comparison of differentially located one-to-one orthologs between C. elegans and P. pacificus indicates lower expression of X-linked orthologs, arguing against X upregulation. These contradicting observations may be reconciled if X upregulation is not a global mechanism but instead acts locally on a subset of tissues and X-linked genes that are dosage sensitive. IN an XY sex-determination system, male and female genomes are identical with the exception of the male-specific Y chromosome, which bears few genes (Charlesworth et al. 2005). This is particularly true when the Y chromosome is thought to be completely lost, as is the case for C. elegans and many other nematodes (Walton 1940). Because gene content is the same, phenotypic differences between males and females, termed "sexual dimorphisms," must be caused by differential gene expression between the two sexes (Connallon and Knowles 2005;Ellegren and Parsch 2007). Throughout the article, such differentially expressed genes are referred to as "sex biased." As males and females have different fitness optima, a trait that is beneficial to one sex can be harmful to the other (termed sexual antagonism) (Rice and Chippindale 2001;Arnqvist 2004;Connallon and Knowles 2005;Ellegren and Parsch 2007;Mank et al. 2008a;Rice 1984). The evolution of sex-biased gene expression is thought to mediate the effects of sexual antagonism and allow for achievement of sex-specific fitness. Previous studies have indicated that anywhere between 30 and 60% of metazoan genes may be sex biased Parisi et al. 2004;Reinke et al. 2004;Yang et al. 2006;Reinius et al. 2008;Small et al. 2009;Innocenti and Morrow 2010;Assis et al. 2012;Reinius et al. 2012;Thomas et al. 2012). Genes with sex-biased exp...

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Sex-Biased Gene Expression and Evolution of the X Chromosome in Nematodes

et al. 2014

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“…Initial studies comparing median expression levels of present day chromosomes, that is, X versus autosomes, lead to conflicting conclusions: when analyzing all expressed genes, the levels of X-linked genes were found to be indistinguishable from those of autosomal genes, while an analysis that excluded lowly expressed genes showed some degree of upregulation of the X chromosome [5][6][7][8]. As expression can vary significantly even between different autosomes, it has been difficult to draw definitive conclusions from these X-to-autosome comparisons [9 ]. To try and circumvent this problem, two groups recently compared X-linked genes with orthologous genes in species, where these genes have remained autosomal, because their sex chromosomes evolved from a different pair of autosomes (e.g.…”

Section: Evolution Of Sex Chromosome Dosage Compensation In Mammalsmentioning

confidence: 99%

“…For example, components of large protein complexes, whose stoichiometry probably needs to be maintained for proper function, show a $2-fold higher median expression when they are located on the X chromosome compared to autosomal protein complex genes [11 ]. Moreover, the comparison of X-linked genes with autosomal orthologs in other species has suggested that autosomal genes, the protein products of which physically interact with those of Xlinked genes, might have actually been downregulated to achieve dosage compensation [9 ]. Therefore, the available evidence suggests that the X chromosome has not necessarily been upregulated in a chromosome-wide fashion.…”

Section: Evolution Of Sex Chromosome Dosage Compensation In Mammalsmentioning

confidence: 99%

“…X inactivation is found in all mammals with the exception of the most ancestral monotreme lineage, which, similarly to birds, do not appear to show global dosage compensation between the sexes [9 ]. In marsupials, X inactivation is imprinted so that the paternal X is inactive in all cells, while placental mammals inactivate one randomly chosen X chromosome in each cell.…”

Section: Evolution Of Sex Chromosome Dosage Compensation In Mammalsmentioning

confidence: 99%

“…Instead, dosage compensation in relation to autosomal genes might have been restricted mainly to certain dosage sensitive genes. However, even the compensation of a subset of genes makes it necessary to equalize X-linked gene dosage between XY males and XX females, which, in mammals, is ensured by X inactivation.X inactivation is found in all mammals with the exception of the most ancestral monotreme lineage, which, similarly to birds, do not appear to show global dosage compensation between the sexes [9 ]. In marsupials, X inactivation is imprinted so that the paternal X is inactive in all cells, while placental mammals inactivate one randomly chosen X chromosome in each cell.…”

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Role and control of X chromosome dosage in mammalian development

Schulz¹,

Heard²

2013

Current Opinion in Genetics & Development

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Many species have evolved sex chromosomes with highly divergent gene content, such as the X and Y chromosomes in mammals. As most non sex-specific genes probably need to be expressed at similar levels in males and females, dosage compensation mechanisms are in place to equalize the gene dosage between the sexes, and possibly also between sex chromosomes and autosomes. In mammals, one out of two X chromosomes is inactivated early during development in a process called X-chromosome inactivation that has been investigated intensively in the 50 years since it was discovered. Less is known about the potential functional roles of X-linked gene dosage, for example in controlling development in a sexspecific manner. In this review, we discuss the evolution of dosage compensation and how it is controlled during embryogenesis of mammals. In addition we will summarize evidence on the potential role of X chromosome number during early development. IntroductionIn many species, sex is determined by sex chromosome composition, such as XY and XX in male and female mammals. The X and Y chromosomes presumably evolved from a pair of autosomes, one of which (the proto-Y) acquired a sex determining gene and subsequently accumulated male beneficial genes. To permanently link these genes to the male sex, the Y chromosome had to cease recombining with the X during meiosis, and this facilitated a progressive loss of Y-linked genes (reviewed in [1]). Therefore for most X-linked genes, only one copy remains, on the X, and this creates a dosage imbalance, both with respect to interacting autosomal genes and between the sexes (XX versus XY). To resolve this dosage imbalance, a variety of dosage compensation mechanisms have evolved (reviewed in [2]). The first step in compensating the loss of Y-linked genes is probably the upregulation of their Xlinked homologs (Ohno's hypothesis [3]). In the wellstudied example of Drosophila this upregulation is restricted to males, thereby restoring both dosage equality between the X chromosome and autosomes, as well as between the sexes. In contrast, worms (Caenorhabditis elegans) and mammals are thought to upregulate the X chromosome in both sexes and therefore require additional mechanisms to balance X-linked gene dosage between males and females. To achieve this, worms downregulate both X's in hermaphrodites (XX), while mammals, on which we focus in this review, silence one of the two X chromosomes in each female cell in a process called Xchromosome inactivation (XCI). Albeit widespread, the extent of dosage compensation between the sexes varies considerably among species. In birds for example, dosage compensation of Z-linked genes is only partial, as males (ZZ) express 1.2-1.4-fold higher levels compared to females (ZW) [2].Although in mammals, dosage compensation for most genes on the X is probably vital, dosage differences might also play a functional role at several levels. In particular, genes that escape X inactivation are thought to contribute to the phenotypic differences between the sexes [4]...

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Sex Chromosome Dosage Compensation

Csankovszki

2019

Encyclopedia of Life Sciences

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Organisms that use a chromosome‐based mechanism for sex determination must contend with the resulting sex‐linked gene dosage imbalance between males and females. While some organisms appear to tolerate gene‐dosage differences, others have evolved compensatory processes. The molecular mechanisms behind dosage compensation are only understood in a few organisms. In the fruit fly Drosophila melanogaster , XY males upregulate X‐linked gene expression two‐fold by a process that involves histone acetylation. Whether other lineages upregulate the male X is currently highly debated. Then in mammals, XX females inactivate one of their two X chromosomes using the long noncoding RNA Xist and repressive chromatin modifications. In the nematode Caenorhabditis elegans , XX hermaphrodites downregulate gene expression from both X chromosomes two‐fold by the action of a protein complex resembling the mitotic chromosome compaction machinery. Detailed studies of these mechanisms provided insights into not just dosage compensation, but the broader field of gene regulation in general. Key Concepts Differences in sex chromosome dose create a gene expression imbalance. Some lineages tolerate sex‐chromosome‐linked imbalances, other lineages evolved mechanisms to compensate for the differences in gene dosage. Complete balance includes balancing the single male X to autosomes and equalising sex‐linked gene dosage between the sexes. The MSL complex binds to the X chromosome in male Drosophila to upregulate gene expression two‐fold. The MSL subunit MOF acetylates lysine 16 on histone H4 in gene bodies, leading to enhancement of transcription elongation. The noncoding RNA Xist is expressed from the inactive X chromosome of female mammals. Xist RNA recruits chromatin‐modifying activities to transcriptionally silence the chromosome. The condensin‐like DCC binds both X chromosomes of hermaphroditic nematodes to dampen gene expression two‐fold. The DCC remodels and compacts the chromosome and recruits histone‐modifying enzymes to limit RNA Polymerase II loading onto the chromosomes.

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Mechanisms and Evolutionary Patterns of Mammalian and Avian Dosage Compensation

Abstract: A large-scale comparative gene expression study reveals the different ways in which the chromosome-wide gene dosage reductions resulting from sex chromosome differentiation events were compensated during mammalian and avian evolution.

Cited by 211 publications

References 55 publications

Sex-Biased Gene Expression and Evolution of the X Chromosome in Nematodes

Sex-Biased Gene Expression and Evolution of the X Chromosome in Nematodes

Role and control of X chromosome dosage in mammalian development

Sex Chromosome Dosage Compensation

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