PgmNr D1474: Patterns of gene expression variation in a natural population of Drosophila melanogaster provide evidence for GRN robustness through compensatory cis trans interactions.

Authors:
J. Fear 1,2 ; L. León-Novelo 3 ; A. Morse 1,2 ; A. Gerken 1,2 ; K. Van Lehmann 5 ; J. Tower 4 ; S. Nuzhdin 4 ; L. McIntyre 1,2


Institutes
1) Molecular Genetics and Microbiology University of Florida, Gainesville, FL; 2) Genetics Institute University of Florida, Gainesville, FL; 3) Department of Biostatistics; University of Texas Health Science Center at Houston-School of Public health, Houston, TX; 4) Molecular and Computation Biology Program, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA; 5) Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY.


Keyword: cis-regulatory logic

Abstract:

Regulatory variation in gene expression can be described by cis and trans genetic components. Here we use RNA-seq data from a panel of Drosophila melanogaster test crosses to compare allelic imbalance (AI) in female head tissue between mated and virgin flies, an environmental change known to affect transcription. Indeed, 3,048 exons (1,610 genes) are differentially expressed in this study. We use a Bayesian model for the detection of AI and control type I error with an intersection test. There are ~200 genes with AI exclusively in mated or virgin flies and on average 34% of genes within a cross, and 54% of all genes across the entire panel show evidence for genetic regulation of transcription. Nearly all differentially regulated genes are affected in cis, with an average of 63% of expression variation explained by the cis effects. Trans effects explain 8% of the variance in AI on average and the interaction between cis and trans explains an average of 10% of the total variance in AI. In both environments cis and trans effects are compensatory in their overall effect, with the opposite signs of effects of the allele coupled 63% of the time. There is a negative association between cis and trans effects (85%) across lines. We hypothesize that the gene expression level perturbed by cis-regulatory mutations is compensated through trans-regulatory mechanisms, e.g. trans and cis by trans factors buffering cis-mutations. In addition, when AI is detected in both environments, cis-mated, cis-virgin, and trans-mated-trans-virgin estimates are highly concordant. We conclude that the GRN are robust and that trans buffering explains robustness.