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MBE Advance Access published online on November 12, 2007

Molecular Biology and Evolution, doi:10.1093/molbev/msm247
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© The Author 2007. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Article

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

Anne Genissel*, Lauren M. McIntyre{dagger},{ddagger}, Marta L. Wayne§,{ddagger} and Sergey V. Nuzhdin*

* Section of Evolution and Ecology, University of California, Davis, California, 95616
{dagger} Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32611
{ddagger} University of Florida Genetics Institute, University of Florida, Gainesville, FL 32611-8525
§ Department of Zoology, University of Florida, Gainesville, FL 32611

Corresponding author: Anne Genissel, Section of Evolution and Ecology, Division of Biological Sciences, University of California at Davis, Davis, CA 95616, Telephone number: (530) 754-9551, Fax number: (530) 752-1449, E-mail: amgenissel{at}ucdavis.edu

Received for publication November 18, 2006. Revision received March 26, 2007. Revision received September 5, 2007. Accepted for publication October 19, 2007.

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.

Key Words: Drosophilacistrans • genomics • transcription


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