scholarly journals Multilayered Tuning of Dosage Compensation and Z-Chromosome Masculinization in the Wood White (Leptidea sinapis) Butterfly

2019 ◽  
Vol 11 (9) ◽  
pp. 2633-2652
Author(s):  
Lars Höök ◽  
Luis Leal ◽  
Venkat Talla ◽  
Niclas Backström
Keyword(s):  
Dosage Compensation ◽  
Developmental Stages ◽  
Current Knowledge ◽  
Gene Dosage ◽  
Model Organisms ◽  
Z Chromosome ◽  
Xy Model ◽  
Expression Levels ◽  
Male Specific Lethal ◽  
Male Specific

AbstractIn species with genetic sex determination, dosage compensation can evolve to equal expression levels of sex-linked and autosomal genes. Current knowledge about dosage compensation has mainly been derived from male-heterogametic (XX/XY) model organisms, whereas less is understood about the process in female-heterogametic systems (ZZ/ZW). In moths and butterflies, downregulation of Z-linked expression in males (ZZ) to match the expression level in females (ZW) is often observed. However, little is known about the underlying regulatory mechanisms, or if dosage compensation patterns vary across ontogenetic stages. In this study, we assessed dynamics of Z-linked and autosomal expression levels across developmental stages in the wood white (Leptidea sinapis). We found that although expression of Z-linked genes in general was reduced compared with autosomal genes, dosage compensation was actually complete for some categories of genes, in particular sex-biased genes, but equalization in females was constrained to a narrower gene set. We also observed a noticeable convergence in Z-linked expression between males and females after correcting for sex-biased genes. Sex-biased expression increased successively across developmental stages, and male-biased genes were enriched on the Z-chromosome. Finally, all five core genes associated with the ribonucleoprotein dosage compensation complex male-specific lethal were detected in adult females, in correspondence with a reduction in the expression difference between autosomes and the single Z-chromosome. We show that tuning of gene dosage is multilayered in Lepidoptera and argue that expression balance across chromosomal classes may predominantly be driven by enrichment of male-biased genes on the Z-chromosome and cooption of available dosage regulators.

The msl-2 dosage compensation gene of Drosophila encodes a putative DNA-binding protein whose expression is sex specifically regulated by Sex-lethal

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3245-3258 ◽  
Author(s):  
G.J. Bashaw ◽  
B.S. Baker
Keyword(s):  
Dna Binding ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Ring Finger ◽  
The Other ◽  
Male Specific Lethal ◽  
Alternatively Spliced ◽  
Sex Lethal ◽  
Specific Regulation ◽  
Male Specific

In Drosophila dosage compensation increases the rate of transcription of the male's X chromosome and depends on four autosomal male-specific lethal genes. We have cloned the msl-2 gene and shown that MSL-2 protein is co-localized with the other three MSL proteins at hundreds of sites along the male polytene X chromosome and that this binding requires the other three MSL proteins. msl-2 encodes a protein with a putative DNA-binding domain: the RING finger. MSL-2 protein is not produced in females and sequences in both the 5′ and 3′ UTRs are important for this sex-specific regulation. Furthermore, msl-2 pre-mRNA is alternatively spliced in a Sex-lethal-dependent fashion in its 5′ UTR.

scholarly journals Aneuploidy and gene expression: is there dosage compensation?

Epigenomics ◽  
2019 ◽  
Vol 11 (16) ◽  
pp. 1827-1837 ◽  
Author(s):  
Shihoko Kojima ◽  
Daniela Cimini
Keyword(s):  
Gene Expression ◽  
Dosage Compensation ◽  
Current Knowledge ◽  
Gene Dosage ◽  
Congenital Defects ◽  
Gene Products ◽  
Epigenetic Changes ◽  
Transcript Levels ◽  
Compensation Mechanisms ◽  
Additional Chromosome

Aneuploidy (i.e., abnormal chromosome number) is the leading cause of miscarriage and congenital defects in humans. Moreover, aneuploidy is ubiquitous in cancer. The deleterious phenotypes associated with aneuploidy are likely a result of the imbalance in the levels of gene products derived from the additional chromosome(s). Here, we summarize the current knowledge on how the presence of extra chromosomes impacts gene expression. We describe studies that have found a strict correlation between gene dosage and transcript levels as wells as studies that have found a less stringent correlation, hinting at the possible existence of dosage compensation mechanisms. We conclude by peering into the epigenetic changes found in aneuploid cells and outlining current knowledge gaps and potential areas of future investigation.

scholarly journals Rapid Evolution of Autosomal Binding Sites of the Dosage Compensation Complex in Drosophila melanogaster and Its Association With Transcription Divergence

2021 ◽  
Vol 12 ◽  
Author(s):  
Aimei Dai ◽  
Yushuai Wang ◽  
Anthony Greenberg ◽  
Zhongqi Liufu ◽  
Tian Tang
Keyword(s):  
Drosophila Melanogaster ◽  
Dosage Compensation ◽  
Binding Sites ◽  
Protein Sequence ◽  
Rapid Evolution ◽  
Close Relative ◽  
Sequence Evolution ◽  
Male Specific Lethal ◽  
Msl Complex ◽  
Male Specific

How pleiotropy influences evolution of protein sequence remains unclear. The male-specific lethal (MSL) complex in Drosophila mediates dosage compensation by 2-fold upregulation of the X chromosome in males. Nevertheless, several MSL proteins also bind autosomes and likely perform functions not related to dosage compensation. Here, we study the evolution of MOF, MSL1, and MSL2 biding sites in Drosophila melanogaster and its close relative Drosophila simulans. We found pervasive expansion of the MSL binding sites in D. melanogaster, particularly on autosomes. The majority of these newly-bound regions are unlikely to function in dosage compensation and associated with an increase in expression divergence between D. melanogaster and D. simulans. While dosage-compensation related sites show clear signatures of adaptive evolution, these signatures are even more marked among autosomal regions. Our study points to an intriguing avenue of investigation of pleiotropy as a mechanism promoting rapid protein sequence evolution.

scholarly journals Sex chromosome dosage compensation in Heliconius butterflies: global yet still incomplete?

2015 ◽  
Author(s):  
James R Walters ◽  
Thomas J Hardcastle ◽  
Chris Jiggins
Keyword(s):  
Dosage Compensation ◽  
Sex Chromosome ◽  
Gene Dosage ◽  
Dosage Effect ◽  
Epigenetic Mechanism ◽  
Z Chromosome ◽  
Specific Gene ◽  
Dosage Effects ◽  
Heliconius Butterflies ◽  
The Impact

The evolution of heterogametic sex chromosome is often ? but not always ? accompanied by the evolution of dosage compensating mechanisms that mitigate the impact of sex-specific gene dosage on levels of gene expression. One emerging view of this process is that such mechanisms may only evolve in male-heterogametic (XY) species but not in female-heterogametic (ZW) species, which will consequently exhibit ?incomplete? sex chromosome dosage compensation. However, some recent results from moths suggest that Lepidoptera (moths and butterflies) may prove to be an exception to this prediction. Here we report an analysis of sex chromosome dosage compensation in Heliconius butterflies, sampling multiple individuals for several different adult tissues (head, abdomen, leg, mouth, and antennae). Methodologically, we introduce a novel application of linear mixed-effects models to assess dosage compensation, offering a unified statistical framework that can estimate effects specific to chromosome, to sex, and their interactions (i.e., a dosage effect). Our results show substantially reduced Z-linked expression relative to autosomes in both sexes, as previously observed in bombycoid moths. This observation is consistent with an increasing body of evidence that at least some species of moths and butterflies possess an epigenetic sex chromosome dosage compensating mechanism that operates by reducing Z chromosome expression in males. However, this mechanism appears to be imperfect in Heliconius, resulting in a modest dosage effect that produces an average 5-20% male-bias on the Z chromosome, depending on the tissue. Strong sex chromosome dosage effects have been previously in a pyralid moth. Thus our results reflect a mixture of previous patterns reported for Lepidoptera and bisect the emerging view that female-heterogametic ZW taxa have incomplete dosage compensation because they lack a chromosome-wide epigenetic mechanism mediating sex chromosome dosage compensation. In the case of Heliconius, sex chromosome dosage effects persist apparently despite such a mechanism. We also analyze chromosomal distributions of sex-biased genes and show an excess of male-biased and a dearth of female-biased genes on the Z chromosome relative to autosomes, consistent with predictions of sexually antagonistic evolution.

scholarly journals Painting of Fourth and the X-Linked 1.688 Satellite in D. melanogaster Is Involved in Chromosome-Wide Gene Regulation

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 323
Author(s):  
Samaneh Ekhteraei-Tousi ◽  
Jacob Lewerentz ◽  
Jan Larsson
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Rapid Evolution ◽  
Regulatory Mechanisms ◽  
Expression Of Genes ◽  
Male Specific Lethal ◽  
Msl Complex ◽  
Specific Regulation ◽  
Male Specific ◽  
Genomic Regions

Chromosome-specific regulatory mechanisms provide a model to understand the coordinated regulation of genes on entire chromosomes or on larger genomic regions. In fruit flies, two chromosome-wide systems have been characterized: The male-specific lethal (MSL) complex, which mediates dosage compensation and primarily acts on the male X-chromosome, and Painting of fourth (POF), which governs chromosome-specific regulation of genes located on the 4th chromosome. How targeting of one specific chromosome evolves is still not understood; but repeated sequences, in forms of satellites and transposable elements, are thought to facilitate the evolution of chromosome-specific targeting. The highly repetitive 1.688 satellite has been functionally connected to both these systems. Considering the rapid evolution and the necessarily constant adaptation of regulatory mechanisms, such as dosage compensation, we hypothesised that POF and/or 1.688 may still show traces of dosage-compensation functions. Here, we test this hypothesis by transcriptome analysis. We show that loss of Pof decreases not only chromosome 4 expression but also reduces the X-chromosome expression in males. The 1.688 repeat deletion, Zhr1 (Zygotic hybrid rescue), does not affect male dosage compensation detectably; however, Zhr1 in females causes a stimulatory effect on X-linked genes with a strong binding affinity to the MSL complex (genes close to high-affinity sites). Lack of pericentromeric 1.688 also affected 1.688 expression in trans and was linked to the differential expression of genes involved in eggshell formation. We discuss our results with reference to the connections between POF, the 1.688 satellite and dosage compensation, and the role of the 1.688 satellite in hybrid lethality.

scholarly journals Modulation of MSL1 Abundance in Female Drosophila Contributes to the Sex Specificity of Dosage Compensation

Genetics ◽  
1998 ◽  
Vol 150 (2) ◽  
pp. 699-709 ◽  
Author(s):  
Kimberly A Chang ◽  
Mitzi I Kuroda
Keyword(s):  
Dosage Compensation ◽  
Ectopic Expression ◽  
Negative Regulation ◽  
Limiting Factor ◽  
Control Mechanisms ◽  
Linked Gene ◽  
Male Specific Lethal ◽  
Sex Specificity ◽  
Female Specific ◽  
Male Specific

Abstract Dosage compensation in Drosophila is the mechanism by which X-linked gene expression is made equal in males and females. Proper regulation of this process is critical to the survival of both sexes. Males must turn the male-specific lethal (msl)-mediated pathway of dosage compensation on and females must keep it off. The msl2 gene is the primary target of negative regulation in females. Preventing production of MSL2 protein is sufficient to prevent dosage compensation; however, ectopic expression of MSL2 protein in females is not sufficient to induce an insurmountable level of dosage compensation, suggesting that an additional component is limiting in females. A candidate for this limiting factor is MSL1, because the amount of MSL1 protein in females is reduced compared to males. We have identified two levels of negative regulation of msl1 in females. The predominant regulation is at the level of protein stability, while a second regulatory mechanism functions at the level of protein synthesis. Overcoming these control mechanisms by overexpressing both MSL1 and MSL2 in females results in 100% female-specific lethality.

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

Development ◽  
1996 ◽  
Vol 122 (9) ◽  
pp. 2751-2760 ◽  
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.

scholarly journals Male-specific lethal complex inDrosophilacounteracts histone acetylation and does not mediate dosage compensation

2013 ◽  
Vol 110 (9) ◽  
pp. E808-E817 ◽  
Author(s):  
Lin Sun ◽  
Harvey R. Fernandez ◽  
Ryan C. Donohue ◽  
Jilong Li ◽  
Jianlin Cheng ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Dosage Compensation ◽  
Male Specific Lethal ◽  
Male Specific Lethal Complex ◽  
Male Specific
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