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What the X has to do with it: differences in regulatory variability between the sexes in Drosophila simulans.

Graze RM, McIntyre LM, Morse AM, Boyd BM, Nuzhdin SV, Wayne ML - Genome Biol Evol (2014)

Bottom Line: However, there are differences between cis and trans effects: cis variants show evidence of purifying selection in the sex toward which expression is biased, while trans variants do not.For female-biased genes, the X is depleted for trans variation in a manner consistent with a female-dominated selection regime on the X.Surprisingly, there is no evidence for depletion of trans variation for male-biased genes on X.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics and Microbiology, University of Florida.

ABSTRACT
The mechanistic basis of regulatory variation and the prevailing evolutionary forces shaping that variation are known to differ between sexes and between chromosomes. Regulatory variation of gene expression can be due to functional changes within a gene itself (cis) or in other genes elsewhere in the genome (trans). The evolutionary properties of cis mutations are expected to differ from mutations affecting gene expression in trans. We analyze allele-specific expression across a set of X substitution lines in intact adult Drosophila simulans to evaluate whether regulatory variation differs for cis and trans, for males and females, and for X-linked and autosomal genes. Regulatory variation is common (56% of genes), and patterns of variation within D. simulans are consistent with previous observations in Drosophila that there is more cis than trans variation within species (47% vs. 25%, respectively). The relationship between sex-bias and sex-limited variation is remarkably consistent across sexes. However, there are differences between cis and trans effects: cis variants show evidence of purifying selection in the sex toward which expression is biased, while trans variants do not. For female-biased genes, the X is depleted for trans variation in a manner consistent with a female-dominated selection regime on the X. Surprisingly, there is no evidence for depletion of trans variation for male-biased genes on X. This is evidence for regulatory feminization of the X, trans-acting factors controlling male-biased genes are more likely to be found on the autosomes than those controlling female-biased genes.

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The distribution of cis and trans variation in transcript abundance. The distribution of the cis (solid line) and trans (dashed line) effect estimates (calculated as the standardized mean difference) for genes with significant regulatory variation are shown for males (blue) and females (red). The left panel shows the distribution for autosomal genes in females (n = 4,103 for cis and n = 1,804 for trans), the middle panel shows the distribution for autosomal genes in males (n = 3,704 for cis and n = 1,399 for trans), and the right panel shows the distribution for X-linked genes in females (n = 501 for cis and n = 250 for trans). For each plot, the Y axis is the frequency and the X axis is the standardized estimate of cis or trans differences between X-substitution parental strain genotypes and the st e reference line.
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evu060-F3: The distribution of cis and trans variation in transcript abundance. The distribution of the cis (solid line) and trans (dashed line) effect estimates (calculated as the standardized mean difference) for genes with significant regulatory variation are shown for males (blue) and females (red). The left panel shows the distribution for autosomal genes in females (n = 4,103 for cis and n = 1,804 for trans), the middle panel shows the distribution for autosomal genes in males (n = 3,704 for cis and n = 1,399 for trans), and the right panel shows the distribution for X-linked genes in females (n = 501 for cis and n = 250 for trans). For each plot, the Y axis is the frequency and the X axis is the standardized estimate of cis or trans differences between X-substitution parental strain genotypes and the st e reference line.

Mentions: Cis and trans estimates were more frequently negative than positive, indicating that there were more cases where the st e derived allele was expressed at a lower level than the other allele. The mean effect sizes of cis and trans effects are the same. However, much larger cis effects than trans effects were detected on the autosomes, and thus the range of effect sizes for cis effects is greater. The range of effect sizes for cis and trans in females on the X is more similar, although there are still twice as many significant cis effects as trans effects (fig. 3). This is unlikely to be due to a difference in power. If mean trans effects are generally smaller than mean cis effects (Genissel et al. 2008; Gruber et al. 2012), one would expect to find only large significant trans effects, as the power to detect trans might be less than for cis. Another possibility is that effect sizes are the same, but there is greater error variance for trans effects than for cis effects. In this case, fewer significant effects of a given size would be detected for trans than for cis would be detected. We find that the average standardized effect sizes for cis and trans are the same, indicating that power to detect differences is similar in this design (fig. 3).Fig. 3.—


What the X has to do with it: differences in regulatory variability between the sexes in Drosophila simulans.

Graze RM, McIntyre LM, Morse AM, Boyd BM, Nuzhdin SV, Wayne ML - Genome Biol Evol (2014)

The distribution of cis and trans variation in transcript abundance. The distribution of the cis (solid line) and trans (dashed line) effect estimates (calculated as the standardized mean difference) for genes with significant regulatory variation are shown for males (blue) and females (red). The left panel shows the distribution for autosomal genes in females (n = 4,103 for cis and n = 1,804 for trans), the middle panel shows the distribution for autosomal genes in males (n = 3,704 for cis and n = 1,399 for trans), and the right panel shows the distribution for X-linked genes in females (n = 501 for cis and n = 250 for trans). For each plot, the Y axis is the frequency and the X axis is the standardized estimate of cis or trans differences between X-substitution parental strain genotypes and the st e reference line.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4007535&req=5

evu060-F3: The distribution of cis and trans variation in transcript abundance. The distribution of the cis (solid line) and trans (dashed line) effect estimates (calculated as the standardized mean difference) for genes with significant regulatory variation are shown for males (blue) and females (red). The left panel shows the distribution for autosomal genes in females (n = 4,103 for cis and n = 1,804 for trans), the middle panel shows the distribution for autosomal genes in males (n = 3,704 for cis and n = 1,399 for trans), and the right panel shows the distribution for X-linked genes in females (n = 501 for cis and n = 250 for trans). For each plot, the Y axis is the frequency and the X axis is the standardized estimate of cis or trans differences between X-substitution parental strain genotypes and the st e reference line.
Mentions: Cis and trans estimates were more frequently negative than positive, indicating that there were more cases where the st e derived allele was expressed at a lower level than the other allele. The mean effect sizes of cis and trans effects are the same. However, much larger cis effects than trans effects were detected on the autosomes, and thus the range of effect sizes for cis effects is greater. The range of effect sizes for cis and trans in females on the X is more similar, although there are still twice as many significant cis effects as trans effects (fig. 3). This is unlikely to be due to a difference in power. If mean trans effects are generally smaller than mean cis effects (Genissel et al. 2008; Gruber et al. 2012), one would expect to find only large significant trans effects, as the power to detect trans might be less than for cis. Another possibility is that effect sizes are the same, but there is greater error variance for trans effects than for cis effects. In this case, fewer significant effects of a given size would be detected for trans than for cis would be detected. We find that the average standardized effect sizes for cis and trans are the same, indicating that power to detect differences is similar in this design (fig. 3).Fig. 3.—

Bottom Line: However, there are differences between cis and trans effects: cis variants show evidence of purifying selection in the sex toward which expression is biased, while trans variants do not.For female-biased genes, the X is depleted for trans variation in a manner consistent with a female-dominated selection regime on the X.Surprisingly, there is no evidence for depletion of trans variation for male-biased genes on X.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics and Microbiology, University of Florida.

ABSTRACT
The mechanistic basis of regulatory variation and the prevailing evolutionary forces shaping that variation are known to differ between sexes and between chromosomes. Regulatory variation of gene expression can be due to functional changes within a gene itself (cis) or in other genes elsewhere in the genome (trans). The evolutionary properties of cis mutations are expected to differ from mutations affecting gene expression in trans. We analyze allele-specific expression across a set of X substitution lines in intact adult Drosophila simulans to evaluate whether regulatory variation differs for cis and trans, for males and females, and for X-linked and autosomal genes. Regulatory variation is common (56% of genes), and patterns of variation within D. simulans are consistent with previous observations in Drosophila that there is more cis than trans variation within species (47% vs. 25%, respectively). The relationship between sex-bias and sex-limited variation is remarkably consistent across sexes. However, there are differences between cis and trans effects: cis variants show evidence of purifying selection in the sex toward which expression is biased, while trans variants do not. For female-biased genes, the X is depleted for trans variation in a manner consistent with a female-dominated selection regime on the X. Surprisingly, there is no evidence for depletion of trans variation for male-biased genes on X. This is evidence for regulatory feminization of the X, trans-acting factors controlling male-biased genes are more likely to be found on the autosomes than those controlling female-biased genes.

Show MeSH
Related in: MedlinePlus