Does postzygotic isolation result from improper dosage compensation?

Abstract The X chromosome invariably has the largest effect on postzygotic isolation between animal species. One explanation of this pattern is that inviability and sterility result from a breakdown in the dosage compensation of X-linked genes in hybrids. In Drosophila, such breakdown could result from divergence of the genes used to assess the X/autosomal (X/A) ratio, and thus the sex, of an individual. I test this hypothesis by introducing mutant alleles of the Sex-lethal locus into Drosophila melanogaster-Drosophila simulans hybrids. These mutants "ignore" any perceived anomalous X/A ratio and thus can be used to ensure proper dosage compensation in hybrids. These mutants do not rescue hybrid viability or fertility, implying that postzygotic isolation in this hybridization does not result from a disruption of dosage compensation caused by divergence of the X/A counting system.

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Transposon insertions causing constitutive Sex-lethal activity in Drosophila melanogaster affect Sxl sex-specific transcript splicing.

Genetics ◽

10.1093/genetics/139.2.631 ◽

1995 ◽

Vol 139 (2) ◽

pp. 631-648

Author(s):

M Bernstein ◽

R A Lersch ◽

L Subrahmanyan ◽

T W Cline

Keyword(s):

Drosophila Melanogaster ◽

X Chromosome ◽

Dosage Compensation ◽

Rna Splicing ◽

Wild Type ◽

Gain Of Function ◽

Positive Regulators ◽

Sex Lethal ◽

Male Specific ◽

Transposon Insertions

Abstract Sex-lethal (Sxl) gene products induce female development in Drosophila melanogaster and suppress the transcriptional hyperactivation of X-linked genes responsible for male X-chromosome dosage compensation. Control of Sxl functioning by the dose of X-chromosomes normally ensures that the female-specific functions of this developmental switch gene are only expressed in diplo-X individuals. Although the immediate effect of X-chromosome dose is on Sxl transcription, during most of the life cycle "on" vs. "off" reflects alternative Sxl RNA splicing, with the female (productive) splicing mode maintained by a positive feedback activity of SXL protein on Sxl pre-mRNA splicing. "Male-lethal" (SxlM) gain-of-function alleles subvert Sxl control by X-chromosome dose, allowing female Sxl functions to be expressed independent of the positive regulators upstream of Sxl. As a consequence, SxlM haplo-X animals (chromosomal males) die because of improper dosage compensation, and SxlM chromosomal females survive the otherwise lethal effects of mutations in upstream positive regulators. Five independent spontaneous SxlM alleles were shown previously to be transposon insertions into what was subsequently found to be the region of regulated sex-specific Sxl RNA splicing. We show that these five alleles represent three different mutant types: SxlM1, SxlM3, and SxlM4. SxlM1 is an insertion of a roo element 674 bp downstream of the translation-terminating male-specific exon. SxlM3 is an insertion of a hobo transposon (not 297 as previously reported) into the 3' splice site of the male exon, and SxlM4 is an insertion of a novel transposon into the male-specific exon itself. We show that these three gain-of-function mutants differ considerably in their ability to bypass the sex determination signal, with SxlM4 being the strongest and SxlM1 the weakest. This difference is also reflected in effects of these mutations on sex-specific RNA splicing and on the rate of appearance of SXL protein in male embryos. Transcript analysis of double-mutant male-viable SxlM derivatives in which the SxlM insertion is cis to loss-of-function mutations, combined with other results reported here, indicates that the constitutive character of these SxlM alleles is a consequence of an alteration of the structure of the pre-mRNA that allows some level of female splicing to occur even in the absence of functional SXL protein. Surprisingly, however, most of the constitutive character of SxlM alleles appears to depend on the mutant alleles' responsiveness, perhaps greater than wild-type, to the autoregulatory splicing activity of the wild-type SXL proteins they produce.

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

Development ◽

10.1242/dev.121.10.3245 ◽

1995 ◽

Vol 121 (10) ◽

pp. 3245-3258 ◽

Cited By ~ 6

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.

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Quantitative Genetics of Drosophila Melanogaster. II. Heritabilities and Genetic Correlations between Sexes for Head and Thorax Traits.

Genetics ◽

10.1093/genetics/119.2.421 ◽

1988 ◽

Vol 119 (2) ◽

pp. 421-433

Author(s):

D E Cowley ◽

W R Atchley

Keyword(s):

Drosophila Melanogaster ◽

Sexual Dimorphism ◽

Genetic Analysis ◽

X Chromosome ◽

Dosage Compensation ◽

Imaginal Disc ◽

Genetic Correlations ◽

Body Parts ◽

Quantitative Genetic ◽

Males And Females

Abstract A quantitative genetic analysis is reported for traits on the head and thorax of adult fruit flies, Drosophila melanogaster. Females are larger than males, and the magnitude of sexual dimorphism is similar for traits derived from the same imaginal disc, but the level of sexual dimorphism varies widely across discs. The greatest difference between males and females occurs for the dimensions of the sclerotized mouthparts of the proboscis. Most of the traits studied are highly heritable with heritabilities ranging from 0.26 to 0.84 for males and 0.27 to 0.81 for females. In general, heritabilities are slightly higher for males, possibly reflecting the effect of dosage compensation on X-linked variance. The X chromosome contributes substantially to variance for many of these traits, and including results reported elsewhere, the variance for over two-thirds of the traits studied includes X-linked variance. The genetic correlations between sexes for the same trait are generally high and close to unity. Coupled with the small differences in the traits between sexes for heritabilities and phenotypic variances, these results suggest that selection would be very slow to change the level of sexual dimorphism in size of various body parts.

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Chromosomal basis of dosage compensation in Drosophila: I. Cellular autonomy of hyperactivity of the male X-chromosome in salivary glands and sex differentiation

Genetics Research ◽

10.1017/s001667230000197x ◽

1969 ◽

Vol 14 (2) ◽

pp. 137-150 ◽

Cited By ~ 43

Author(s):

S. C. Lakhotia ◽

A. S. Mukherjee

Keyword(s):

Drosophila Melanogaster ◽

Salivary Glands ◽

X Chromosome ◽

Metabolic Activity ◽

Dosage Compensation ◽

Rna Synthesis ◽

Sex Differentiation ◽

Chromosome 3 ◽

Normal Male ◽

Developmental Physiology

Morphology and the rate of RNA synthesis of the X-chromosome in XX/XO mosaic larval salivary glands of Drosophila melanogaster have been examined. For this purpose the unstable ring-X was utilized to produce XX and XO nuclei in the same pair of glands. The width of the X-chromosome and the left arm of the 3rd chromosome (3L) of larval salivary glands was measured and the rate of RNA synthesis by them was studied upon the use of [3H]uridine autoradiography in such XX (female) and XO (male) nuclei developing in a female background (i.e. otherwise genotypically XX). In such mosaic glands the width of the single X-chromosome of male nuclei is nearly as great as that of the paired two X's of female nuclei, as is also the case in normal male (X Y) and female (XX). The single X of male nuclei synthesizes RNA at a rate equal to that of the paired two X's of female nuclei and nearly twice that of an unpaired X of XX nuclei. Neither the developmental physiology of the sex nor the proportion of XO nuclei in a pair of mosaic salivary glands of an XX larva has any influence on these two characteristics of the male X-chromosome.It is suggested that dosage compensation in Drosophila is achieved chiefly, if not fully, by a hyperactivity of the male X, in contrast to the single X inactivation in female mammals, that this hyperactivity of the male X is expressed visibly in the morphology and metabolic activity of the X-chromosome in the larval salivary glands of the male, and that this hyperactivity and therefore dosage compensation in Drosophila in general is not dependent on sex-differentiation, but is a function of the doses of the X-chromosome itself.

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Dosage Compensation in Drosophila: Evidence That daughterless and Sex-lethal Control X Chromosome Activity at the Blastoderm Stage of Embryogenesis

Genetics ◽

10.1093/genetics/117.3.477 ◽

1987 ◽

Vol 117 (3) ◽

pp. 477-485

Author(s):

J Peter Gergen

Keyword(s):

X Chromosome ◽

Dosage Compensation ◽

Lethal Gene ◽

Gene Products ◽

Lethal Control ◽

Eye Color ◽

Phenotypic Assay ◽

Sex Lethal ◽

Blastoderm Stage

ABSTRACT Dosage compensation is a mechanism that equalizes the expression of X chromosome linked genes in males, who have one X chromosome, with that in females, who have two. In Drosophila, this is achieved by the relative hyperactivation of X-linked genes in males, as was first shown by Muller using a phenotypic assay based on adult eye color. Several genes involved in regulating dosage compensation have been identified through the isolation of mutations that are sex-specific lethals. However, because of this lethality it is not straightforward to assay the relative roles of these genes using assays based on adult phenotypes. Here this problem is circumvented using an assay based on embryonic phenotypes. These experiments indicate that dosage compensation is established early in development and demonstrate that the daughterless and Sex-lethal gene products are involved in regulating X chromosome activity at the blastoderm stage of embryogenesis.

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Autosomal and X-Linked Additive Genetic Variation for Lifespan and Aging: Comparisons Within and Between the Sexes in Drosophila melanogaster

G3 Genes|Genome|Genetics ◽

10.1534/g3.116.028308 ◽

2016 ◽

Vol 6 (12) ◽

pp. 3903-3911 ◽

Cited By ~ 7

Author(s):

Robert M Griffin ◽

Holger Schielzeth ◽

Urban Friberg

Keyword(s):

Drosophila Melanogaster ◽

Genetic Variation ◽

X Chromosome ◽

Dosage Compensation ◽

Genetic Variance ◽

Additive Genetic Variance ◽

Conclusive Evidence ◽

Substitution Lines ◽

Chromosome Substitution Lines ◽

Sexually Antagonistic Selection

Abstract Theory makes several predictions concerning differences in genetic variation between the X chromosome and the autosomes due to male X hemizygosity. The X chromosome should: (i) typically show relatively less standing genetic variation than the autosomes, (ii) exhibit more variation in males compared to females because of dosage compensation, and (iii) potentially be enriched with sex-specific genetic variation. Here, we address each of these predictions for lifespan and aging in Drosophila melanogaster. To achieve unbiased estimates of X and autosomal additive genetic variance, we use 80 chromosome substitution lines; 40 for the X chromosome and 40 combining the two major autosomes, which we assay for sex-specific and cross-sex genetic (co)variation. We find significant X and autosomal additive genetic variance for both traits in both sexes (with reservation for X-linked variation of aging in females), but no conclusive evidence for depletion of X-linked variation (measured through females). Males display more X-linked variation for lifespan than females, but it is unclear if this is due to dosage compensation since also autosomal variation is larger in males. Finally, our results suggest that the X chromosome is enriched for sex-specific genetic variation in lifespan but results were less conclusive for aging overall. Collectively, these results suggest that the X chromosome has reduced capacity to respond to sexually concordant selection on lifespan from standing genetic variation, while its ability to respond to sexually antagonistic selection may be augmented.

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A Role for siRNA in X-Chromosome Dosage Compensation in Drosophila melanogaster

Genetics ◽

10.1534/genetics.112.140236 ◽

2012 ◽

Vol 191 (3) ◽

pp. 1023-1028 ◽

Cited By ~ 28

Author(s):

Debashish U. Menon ◽

Victoria H. Meller

Keyword(s):

Drosophila Melanogaster ◽

X Chromosome ◽

Dosage Compensation

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LACK OF DOSAGE COMPENSATION FOR AN AUTOSOMAL GENE RELOCATED TO THE X CHROMOSOME IN DROSOPHILA MELANOGASTER

Genetics ◽

10.1093/genetics/85.3.489 ◽

1977 ◽

Vol 85 (3) ◽

pp. 489-496

Author(s):

Richard L Roehrdanz ◽

James M Kitchens ◽

John C Lucchesi

Keyword(s):

Drosophila Melanogaster ◽

Experimental Evidence ◽

Structural Gene ◽

X Chromosome ◽

Dosage Compensation ◽

Oxidase Activity ◽

Aldehyde Oxidase ◽

Autosomal Gene

ABSTRACT Aldehyde oxidase activity has been measured in flies with the structural gene for this enzyme translocated to the X chromosome. These measurements are presented as experimental evidence that, in Drosophila melanogaster, an autosomal gene relocated to the X chromosome is not dosage compensated.

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The MSL3 chromodomain directs a key targeting step for dosage compensation of the Drosophila melanogaster X chromosome

Nature Structural & Molecular Biology ◽

10.1038/nsmb.1520 ◽

2008 ◽

Vol 15 (12) ◽

pp. 1318-1325 ◽

Cited By ~ 63

Author(s):

Tuba H Sural ◽

Shouyong Peng ◽

Bing Li ◽

Jerry L Workman ◽

Peter J Park ◽

...

Keyword(s):

Drosophila Melanogaster ◽

X Chromosome ◽

Dosage Compensation

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The Influence of Chromosomal Environment on X-Linked Gene Expression in Drosophila melanogaster

Genome Biology and Evolution ◽

10.1093/gbe/evaa227 ◽

2020 ◽

Vol 12 (12) ◽

pp. 2391-2402

Author(s):

Aleksei Belyi ◽

Eliza Argyridou ◽

John Parsch

Keyword(s):

Gene Expression ◽

Drosophila Melanogaster ◽

Binding Site ◽

X Chromosome ◽

Dosage Compensation ◽

Negative Correlation ◽

Expression Ratio ◽

Linked Gene ◽

Somatic Tissues ◽

Male To Female

Abstract Sex chromosomes often differ from autosomes with respect to their gene expression and regulation. In Drosophila melanogaster, X-linked genes are dosage compensated by having their expression upregulated in the male soma, a process mediated by the X-chromosome-specific binding of the dosage compensation complex (DCC). Previous studies of X-linked gene expression found a negative correlation between a gene’s male-to-female expression ratio and its distance to the nearest DCC binding site in somatic tissues, including head and brain, which suggests that dosage compensation influences sex-biased gene expression. A limitation of the previous studies, however, was that they focused on endogenous X-linked genes and, thus, could not disentangle the effects of chromosomal position from those of gene-specific regulation. To overcome this limitation, we examined the expression of an exogenous reporter gene inserted at many locations spanning the X chromosome. We observed a negative correlation between the male-to-female expression ratio of the reporter gene and its distance to the nearest DCC binding site in somatic tissues, but not in gonads. A reporter gene’s location relative to a DCC binding site had greater influence on its expression than the local regulatory elements of neighboring endogenous genes, suggesting that intra-chromosomal variation in the strength of dosage compensation is a major determinant of sex-biased gene expression. Average levels of sex-biased expression did not differ between head and brain, but there was greater positional effect variation in the brain, which may explain the observed excess of endogenous sex-biased genes located on the X chromosome in this tissue.

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