X chromosomes show a faster evolutionary rate and complete somatic dosage compensation across Timema stick insect species

Sex chromosomes have evolved repeatedly across the tree of life. As they are present in different copy numbers in males and females, they are expected to experience different selection pressures than the autosomes, with consequences including a faster rate of evolution, increased accumulation of sexually antagonistic alleles, and the evolution of dosage compensation. Whether these consequences are general or linked to idiosyncrasies of specific taxa is not clear as relatively few taxa have been studied thus far. Here we use whole-genome sequencing to identify and characterize the evolution of the X chromosome in five species of Timema stick insects with XX:X0 sex determination. The X chromosome had a similar size (approximately 11% of the genome) and gene content across all five species, suggesting that the X chromosome originated prior to the diversification of the genus. Genes on the X showed evidence of a faster evolutionary rate than genes on the autosomes, likely due to less effective purifying selection. Genes on the X also showed almost complete dosage compensation in somatic tissues (heads and legs), but dosage compensation was absent in the reproductive tracts. Contrary to prediction, sex-biased genes showed little enrichment on the X, suggesting that the advantage X-linkage provides to the accumulation of sexually antagonistic alleles is weak. Overall, we found the consequences of X-linkage on gene sequences and expression to be similar across Timema species, showing the characteristics of the X chromosome are surprisingly consistent over 30 million years of evolution.

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Absence of X-chromosome dosage compensation in the primordial germ cells of Drosophila embryos

Scientific Reports ◽

10.1038/s41598-021-84402-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ryoma Ota ◽

Makoto Hayashi ◽

Shumpei Morita ◽

Hiroki Miura ◽

Satoru Kobayashi

Keyword(s):

X Chromosome ◽

Germ Cells ◽

Dosage Compensation ◽

Sex Chromosome ◽

Primordial Germ Cells ◽

Histone H4 ◽

X Chromosomes ◽

Essential Components ◽

Msl Complex ◽

Male Specific

AbstractDosage compensation is a mechanism that equalizes sex chromosome gene expression between the sexes. In Drosophila, individuals with two X chromosomes (XX) become female, whereas males have one X chromosome (XY). In males, dosage compensation of the X chromosome in the soma is achieved by five proteins and two non-coding RNAs, which assemble into the male-specific lethal (MSL) complex to upregulate X-linked genes twofold. By contrast, it remains unclear whether dosage compensation occurs in the germline. To address this issue, we performed transcriptome analysis of male and female primordial germ cells (PGCs). We found that the expression levels of X-linked genes were approximately twofold higher in female PGCs than in male PGCs. Acetylation of lysine residue 16 on histone H4 (H4K16ac), which is catalyzed by the MSL complex, was undetectable in these cells. In male PGCs, hyperactivation of X-linked genes and H4K16ac were induced by overexpression of the essential components of the MSL complex, which were expressed at very low levels in PGCs. Together, these findings indicate that failure of MSL complex formation results in the absence of X-chromosome dosage compensation in male PGCs.

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Parallel Universes for Models of X Chromosome Dosage Compensation in Drosophila: A Review

Cytogenetic and Genome Research ◽

10.1159/000445924 ◽

2016 ◽

Vol 148 (1) ◽

pp. 52-67 ◽

Cited By ~ 11

Author(s):

James A. Birchler

Keyword(s):

X Chromosome ◽

Dosage Compensation ◽

Sex Chromosome ◽

Fold Increase ◽

Molecular Data ◽

X Chromosomes ◽

Histone Modifiers ◽

Parallel Universes ◽

Msl Complex ◽

High Level

Dosage compensation in Drosophila involves an approximately 2-fold increase in expression of the single X chromosome in males compared to the per gene expression in females with 2 X chromosomes. Two models have been considered for an explanation. One proposes that the male-specific lethal (MSL) complex that is associated with the male X chromosome brings histone modifiers to the sex chromosome to increase its expression. The other proposes that the inverse effect which results from genomic imbalance would tend to upregulate the genome approximately 2-fold, but the MSL complex sequesters histone modifiers from the autosomes to the X to mute this autosomal male-biased expression. On the X, the MSL complex must override the high level of resulting histone modifications to prevent overcompensation of the X chromosome. Each model is evaluated in terms of fitting classical genetic and recent molecular data. Potential paths toward resolving the models are suggested.

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SDC-3 coordinates the assembly of a dosage compensation complex on the nematode X chromosome

Development ◽

10.1242/dev.124.5.1019 ◽

1997 ◽

Vol 124 (5) ◽

pp. 1019-1031 ◽

Cited By ~ 1

Author(s):

T.L. Davis ◽

B.J. Meyer

Keyword(s):

Zinc Finger ◽

X Chromosome ◽

Dosage Compensation ◽

Protein Complex ◽

Terminal Region ◽

X Chromosomes ◽

C Elegans ◽

Amino Terminal ◽

Zinc Finger Motifs ◽

Specific Association

X chromosome expression in C. elegans is controlled by a chromosome-wide regulatory process called dosage compensation that specifically reduces by half the level of transcripts made from each hermaphrodite X chromosome. This process equalizes X expression between the sexes (XX hermaphrodites and XO males), despite their two-fold difference in X chromosome dose, and thereby prevents sex-specific lethality. Dosage compensation is achieved by a protein complex that associates with X in a sex-specific fashion to modulate gene expression. SDC-3, a protein that coordinately controls both sex determination and dosage compensation, activates dosage compensation by directing the dosage compensation protein complex to the hermaphrodite X chromosomes. We show that SDC-3 coordinates this assembly through its own sex-specific association with X. SDC-3 in turn requires other members of the dosage compensation gene hierarchy for its stability and its X localization. In addition, SDC-3 requires its own zinc finger motifs and an amino-terminal region for its X association. Our experiments suggest the possible involvement of zinc finger motifs in X chromosome recognition and the amino-terminal region in interactions with other dosage compensation proteins.

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Gene action in the mammalian X-chromosome

Genetics Research ◽

10.1017/s0016672300010624 ◽

1967 ◽

Vol 9 (3) ◽

pp. 343-357 ◽

Cited By ~ 13

Author(s):

Hans Grüneberg

Keyword(s):

X Chromosome ◽

Dosage Compensation ◽

Gene Action ◽

X Chromosomes ◽

Independent Evidence ◽

Partial Inhibition ◽

Lyon Hypothesis ◽

New Hypothesis

Contrary to opinions expressed by various authors, the phenotype of heterozygotes for mammalian sex-linked genes gives no support for the Lyon hypothesis (L.H.). Evidence, mainly from the mouse, shows that in such heterozygotes, both alleles act together as in autosomal genes.In the present paper, it is shown that neither the behaviour of double heterozygotes for sex-linked genes nor that of X-autosome translocations provides independent evidence in favour of the L.H.: in each case, the interpretation depends on that of the behaviour of single heterozygotes and hence fails to discriminate. Moreover, new facts from both types of situation are also contrary to the L.H. In particular, a unified interpretation which fits the behaviour of genes in all known types of X-autosome translocations in the mouse requires the assumption that partial inhibition of gene action happens in both X-chromosomes of mouse females, and presumably the females of other mammals. The new hypothesis is consistent with all relevant genetical facts and, like the L.H., it also accounts for dosage compensation.

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GA-repeats on mammalian X chromosomes support Ohno’s hypothesis of dosage compensation by transcriptional upregulation

10.1101/485300 ◽

2018 ◽

Author(s):

Edridge D’Souza ◽

Elizaveta Hosage ◽

Kathryn Weinand ◽

Steve Gisselbrecht ◽

Vicky Markstein ◽

...

Keyword(s):

Gene Expression ◽

Transposable Elements ◽

X Chromosome ◽

Dosage Compensation ◽

Binding Sites ◽

Convergent Evolution ◽

Fruit Fly ◽

Dosage Compensation Complex ◽

X Chromosomes ◽

Repeat Sequences

ABSTRACTOver 50 years ago, Susumo Ohno proposed that dosage compensation in mammals would require upregulation of gene expression on the single active X chromosome, a mechanism which to date is best understood in the fruit fly Drosophila melanogaster. Here, we report that the GA-repeat sequences that recruit the conserved MSL dosage compensation complex to the Drosophila X chromosome are also enriched across mammalian X chromosomes, providing genomic support for the Ohno hypothesis. We show that mammalian GA-repeats derive in part from transposable elements, suggesting a mechanism whereby unrelated X chromosomes from dipterans to mammals accumulate binding sites for the MSL dosage compensation complex through convergent evolution, driven by their propensity to accumulate transposable elements.

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Dosage compensation in sciarids is achieved by hypertranscription of the single X chromosome in males.

Genetics ◽

10.1093/genetics/138.3.787 ◽

1994 ◽

Vol 138 (3) ◽

pp. 787-790

Author(s):

P R da Cunha ◽

B Granadino ◽

A L Perondini ◽

L Sánchez

Keyword(s):

X Chromosome ◽

Dosage Compensation ◽

Sex Chromosomes ◽

Sex Chromosome ◽

X Chromosomes ◽

Different Doses

Abstract Dosage compensation refers to the process whereby females and males with different doses of sex chromosomes have similar amounts of products from sex chromosome-linked genes. We analyzed the process of dosage compensation in Sciara ocellaris, Diptera of the suborder Nematocera. By autoradiography and measurements of X-linked rRNA in females (XX) and males (XO), we found that the rate of transcription of the single X chromosome in males is similar to that of the two X chromosomes in females. This, together with the bloated appearance of the X chromosome in males, support the idea that in sciarids dosage compensation is accomplished by hypertranscription of the X chromosome in males.

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Distinct mechanisms mediate X chromosome dosage compensation in Anopheles and Drosophila

Life Science Alliance ◽

10.26508/lsa.202000996 ◽

2021 ◽

Vol 4 (9) ◽

pp. e202000996

Author(s):

Claudia Isabelle Keller Valsecchi ◽

Eric Marois ◽

M Felicia Basilicata ◽

Plamen Georgiev ◽

Asifa Akhtar

Keyword(s):

X Chromosome ◽

Dosage Compensation ◽

Gene Dosage ◽

Histone H4 ◽

Ecological Constraints ◽

Evolutionary Trajectory ◽

X Chromosomes ◽

Deleterious Gene ◽

Msl Complex ◽

High Degree

Sex chromosomes induce potentially deleterious gene expression imbalances that are frequently corrected by dosage compensation (DC). Three distinct molecular strategies to achieve DC have been previously described in nematodes, fruit flies, and mammals. Is this a consequence of distinct genomes, functional or ecological constraints, or random initial commitment to an evolutionary trajectory? Here, we study DC in the malaria mosquito Anopheles gambiae. The Anopheles and Drosophila X chromosomes evolved independently but share a high degree of homology. We find that Anopheles achieves DC by a mechanism distinct from the Drosophila MSL complex–histone H4 lysine 16 acetylation pathway. CRISPR knockout of Anopheles msl-2 leads to embryonic lethality in both sexes. Transcriptome analyses indicate that this phenotype is not a consequence of defective X chromosome DC. By immunofluorescence and ChIP, H4K16ac does not preferentially enrich on the male X. Instead, the mosquito MSL pathway regulates conserved developmental genes. We conclude that a novel mechanism confers X chromosome up-regulation in Anopheles. Our findings highlight the pluralism of gene-dosage buffering mechanisms even under similar genomic and functional constraints.

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Identification of X chromosome regions in Caenorhabditis elegans that contain sex-determination signal elements.

Genetics ◽

10.1093/genetics/138.4.1105 ◽

1994 ◽

Vol 138 (4) ◽

pp. 1105-1125

Author(s):

C C Akerib ◽

B J Meyer

Keyword(s):

Caenorhabditis Elegans ◽

Sex Determination ◽

X Chromosome ◽

Dosage Compensation ◽

X Chromosomes ◽

Sensitive Region ◽

Signal Element ◽

Number Of Genes ◽

Mutant Phenotypes ◽

Chromosome Regions

Abstract The primary sex-determination signal of Caenorhabditis elegans is the ratio of X chromosomes to sets of autosomes (X/A ratio). This signal coordinately controls both sex determination and X chromosome dosage compensation. To delineate regions of X that contain counted signal elements, we examined the effect on the X/A ratio of changing the dose of specific regions of X, using duplications in XO animals and deficiencies in XX animals. Based on the mutant phenotypes of genes that are controlled by the signal, we expected that increases (in males) or decreases (in hermaphrodites) in the dose of X chromosome elements could cause sex-specific lethality. We isolated duplications and deficiencies of specific X chromosome regions, using strategies that would permit their recovery regardless of whether they affect the signal. We identified a dose-sensitive region at the left end of X that contains X chromosome signal elements. XX hermaphrodites with only one dose of this region have sex determination and dosage compensation defects, and XO males with two doses are more severely affected and die. The hermaphrodite defects are suppressed by a downstream mutation that forces all animals into the XX mode of sex determination and dosage compensation. The male lethality is suppressed by mutations that force all animals into the XO mode of both processes. We were able to subdivide this region into three smaller regions, each of which contains at least one signal element. We propose that the X chromosome component of the sex-determination signal is the dose of a relatively small number of genes.

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Evidence that MSL-mediated dosage compensation in Drosophila begins at blastoderm

Development ◽

10.1242/dev.122.9.2751 ◽

1996 ◽

Vol 122 (9) ◽

pp. 2751-2760 ◽

Cited By ~ 1

Author(s):

A. Franke ◽

A. Dernburg ◽

G.J. Bashaw ◽

B.S. Baker

Keyword(s):

X Chromosome ◽

Dosage Compensation ◽

Dependent Manner ◽

Gene Products ◽

Histone H4 ◽

Single Male ◽

Somatic Tissues ◽

Male Specific Lethal ◽

Male Specific ◽

Blastoderm Stage

In Drosophila equalization of the amounts of gene products produced by X-linked genes in the two sexes is achieved by hypertranscription of the single male X chromosome. This process, dosage compensation, is controlled by a set of male-specific lethal (msl) genes, that appear to act at the level of chromatin structure. The properties of the MSL proteins have been extensively studied in the polytene salivary gland chromosomes where they bind to the same set of sites along the male X chromosome in a co-dependent manner. Here we report experiments that show that the MSL proteins first associate with the male X chromosome as early as blastoderm stage, slightly earlier than the histone H4 isoform acetylated at lysine 16 is detected on the X chromosome. MSL binding to the male X chromosome is observed in all somatic tissues of embryos and larvae. Binding of the MSLs to the X chromosome is also interdependent in male embryos and prevented in female embryos by the expression of Sex-lethal (Sxl). A delayed onset of binding of the MSLs in male progeny of homozygous mutant msl-1 or mle mothers coupled with the previous finding that such males have an earlier lethal phase supports the idea that msl-mediated dosage compensation begins early in embryogenesis. Other results show that the maleless (MLE) protein on embryo and larval chromosomes differs in its reactivity with antibodies; the functional significance of this finding remains to be explored.

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Regulation of X-chromosome dosage compensation in human: mechanisms and model systems

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2016.0363 ◽

2017 ◽

Vol 372 (1733) ◽

pp. 20160363 ◽

Cited By ~ 18

Author(s):

Anna Sahakyan ◽

Kathrin Plath ◽

Claire Rougeulle

Keyword(s):

X Chromosome ◽

Dosage Compensation ◽

Sex Chromosome ◽

X Chromosome Inactivation ◽

Human Cells ◽

Model Systems ◽

Chromosome Inactivation ◽

Embryo Research ◽

X Chromosomes ◽

Mary Lyon

The human blastocyst forms 5 days after one of the smallest human cells (the sperm) fertilizes one of the largest human cells (the egg). Depending on the sex-chromosome contribution from the sperm, the resulting embryo will either be female, with two X chromosomes (XX), or male, with an X and a Y chromosome (XY). In early development, one of the major differences between XX female and XY male embryos is the conserved process of X-chromosome inactivation (XCI), which compensates gene expression of the two female X chromosomes to match the dosage of the single X chromosome of males. Most of our understanding of the pre-XCI state and XCI establishment is based on mouse studies, but recent evidence from human pre-implantation embryo research suggests that many of the molecular steps defined in the mouse are not conserved in human. Here, we will discuss recent advances in understanding the control of X-chromosome dosage compensation in early human embryonic development and compare it to that of the mouse. This article is part of the themed issue ‘X-chromosome inactivation: a tribute to Mary Lyon’.

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