Originally published as Genetics Published Articles Ahead of Print on February 3, 2008.

Genetics, Vol. 178, 1831-1835, March 2008, Copyright © 2008
doi:10.1534/genetics.107.082032

Independent Effects of cis- and trans-regulatory Variation on Gene Expression in Drosophila melanogaster

Patricia J. Wittkopp*,{dagger},1, Belinda K. Haerum*,{dagger} and Andrew G. Clark{dagger}

* Department of Ecology and Evolutionary Biology and Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109 and {dagger} Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853

1 Corresponding author: 1061 Kraus Natural Sciences Bldg., 830 N. University Ave., University of Michigan, Ann Arbor, MI 48109-1048.
E-mail: wittkopp{at}umich.edu

Biochemical interactions between cis-regulatory DNA sequences and trans-regulatory gene products suggest that cis- and trans-acting polymorphisms may interact genetically. Here we present a strategy to test this hypothesis by comparing the relative cis-regulatory activity of two alleles in different genetic backgrounds. Of the eight genes surveyed in this study, five were affected by trans-acting variation that altered total transcript levels, two of which were also affected by differences in cis-regulation. The presence of trans-acting variation had no effect on relative cis-regulatory activity, showing that cis-regulatory polymorphisms can function independently of trans-regulatory variation. The frequency of such independent interactions on a genomic scale is yet to be determined.