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Mutational Variation in Gene Expression

ABSTRACT: Transcript abundance was measured in whole-body virgin male Drosophila serrata from 41 inbred lines that had diverged through 27 generations of mutation accumulation. Pleiotropic mutations are the ultimate source of genetic variation in complex traits, including many human diseases. However, the nature and extent of mutational pleiotropy remain largely unknown. Here, we investigate the variation in 11,604 gene expression traits among 41 mutation accumulation lines of Drosophila serrata, which had diverged for 27 generations. We detected significant mutational variance in 4.6% of ESTs, but 70% of ESTs were invariant among lines, allowing us to reject a null hypothesis of phenome-wide universal pleiotropy. Mutational covariance among ESTs was detected at a frequency of only 1 in 193 random pairs of variable EST, bu t was detected among random combinations of five ESTs in 1 in 5 cases, revealing that mutational covariance among multiple ESTs was common. The observed frequency of significant multivariate covariance among random ESTs implied that a substantial number of ESTs (>70) must be pleiotropically affected by at least some mutations.

ORGANISM(S): Drosophila serrata

PROVIDER: GSE49815 | GEO | 2013/09/01

SECONDARY ACCESSION(S): PRJNA214980

REPOSITORIES: GEO

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Project description:Transcript abundance was measured in whole-body virgin male Drosophila serrata from 41 inbred lines that had diverged through 27 generations of mutation accumulation that were sexually selected Sexual selection is predicted to have widespread effects on the genetic variation generated by new mutations as a consequence of the genic capture of condition by male sexual traits. We manipulated the opportunity for sexual selection on males during 27 generations of mutation accumulation in inbred lines of Drosophila serrata, and used a microarray platform to investigate the effect of sexual selection on the expression of 2685 genes, representing a broad coverage of biological function. Sexual selection had little effect on mean gene expression levels, with only 4 genes diverging significantly at a false discovery rate of 5% . In contrast, sexual selection impacted on both the magnitude and nature of mutational variance accumulating in these genes. The magnitude of mutational variance increased under sexual selection by an average of 29%. Mutational variance was less commonly generated by extreme phenotypes less commonly under sexual selection. Furthermore, analysis of random sets of five genes revealed that the mutational variance that accumulated under sexual selection was less pleiotropic in nature than that found in the absence of sexual selection. The generation of greater mutational variance without a general concomitant change in mean expression under sexual selection suggested that gene expression traits were be under apparent rather than direct sexual selection. We discuss two main explanations for the broad-based increase in mutational variance under sexual selection that both require extensive pleiotropy between traits affecting male mating success, standard metric traits represented here by gene expression traits, and general fitness. We measured gene expression of male Drosophila serrata from 41 mutation accumulation lines (whole-body) that were sexually selected. Data from two replicates for each line are presented.

Project description:Pleiotropy is an important biological phenomenon with complicated genetic architectures for multiple traits. To date, pleiotropy was mainly identified by multi-trait GWAS, but GWAS method has its disadvantages, and new developments for pleiotropy detection methods are needed. Here we defined a novel metric, self-product, and based on it, we developed a transcriptome method to identify candidate pleiotropic genes and revealed the genetic architectures of immune and growth trait pairs in pigs. In statistics, the well-known covariance is used to quantify the co-variation between two variables. Suppose that X and Y represent two traits with individual records of xi and yi and corresponding means of μx and μy. We defined the individual-level product (xi − μx)(yi − μy) as self-product. Obviously, self-product is an individual-level measurement for the co-variation between two traits of the ith individual, and the covariance Cov(X , Y) is the mean of the self-product (xi − μx)(yi − μy). The self-product-based transcriptome method was tested using immune and growth trait pairs in pigs.We identify candidate pleiotropic genes using the Affymetrix Porcine Genechip. Result:Comparative transcriptome analyses identified dozens of candidate pleiotropic genes related to 8 trait pairs from two tails of self-product distribution. GO enrichment analysis indicated that most of identified pleiotropic genes were involved in both immune- and growth-related biological processes. We established pleiotropic genes interaction network to exhibit core genes shared by 8 trait pairs, of which CCL5 and IL-10 genes were hub genes. Genetic association analyses showed that SmaI-polymorphisms of CCL5 and IL-10 genes had significant associations with phenotypic co-variations of multiple trait pairs, indicating that the variants in pleiotropic genes were also pleiotropic variants. Conclusions:The validity of our proposed method was preliminarily verified, and our findings provide new insights into the genetic basis of pleiotropic architectures of immune and growth trait pairs in pigs.

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Mutational Variation in Gene Expression

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