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Cis and trans regulatory effects contribute to natural variation in transcriptome of Drosophila melanogaster

by: Anne Genissel, Lauren M Mcintyre, Marta L Wayne, Sergey V Nuzhdin
Mol Biol Evol, Vol. 25, No. 1. (12 January 2008), pp. 101-110.


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The dissection of intraspecific variation in transcriptome is a central theme of many recent quantitative genomic analyses. Transcript level variation has been attributed to factors at the gene itself (cis) and elsewhere in the genome (trans). Previous analyses of Drosophila intraspecific transcriptome variation pointed towards a larger contribution of trans factors. However, data from other genera, and from interspecific comparisons within Drosophila, are more consistent with a major role for cis factors. We investigated the relative amount of cis and trans variation in D. melanogaster, using whole genome expression from an oligonucleotide microarray in the two extensively studied genotypes Ore and 2b3, and six recombinant inbred (RI) lines derived from these parents. We examined two types of models to decompose cis and trans contributions to genetic variation in transcript level: i) an infinitesimal model assuming that the transcription variation is highly polygenic and due to many small effects; and ii) contrast models assuming that a few large effects contribute to the transcriptional variation. We explicitly fitted cis-by-trans interactions, and extended our analyses to consider regulation of alternatively spliced transcripts. We estimated that approximately 10% of the transcriptome was differentially regulated among the lines. We were able to identify cis and trans effects that contribute to this differential regulation for 1340 genes. Our analyses revealed numerous cis effects (90%) but much fewer trans effects, perhaps due to reduced power of detection for trans effects. In addition, we identified fifteen genes which have alternative splice variants differentially regulated in cis. 10.1093/molbev/msm247


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