Originally published as Genetics Published Articles Ahead of Print on December 8, 2008.

Genetics, Vol. 181, 661-670, February 2009, Copyright © 2009
doi:10.1534/genetics.108.098459

Cis-regulatory Variation Is Typically Polyallelic in Drosophila

Jonathan D. Gruber1 and Anthony D. Long

Ecology and Evolutionary Biology, University of California, Irvine, California 92697

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

Gene expression levels vary heritably, with ~25–35% of the loci affecting expression acting in cis. We characterized standing cis-regulatory variation among 16 wild-derived strains of Drosophila melanogaster. Our experiment's robust biological and technical replication enabled precise estimates of variation in allelic expression on a high-throughput SNP genotyping platform. We observed concordant, significant differential allelic expression (DAE) in 7/10 genes queried with multiple SNPs, and every member of a set of eight additional, one-assay genes suggest significant DAE. Four of the high-confidence, multiple-assay genes harbor three or more statistically distinguishable allelic classes, often at intermediate frequency. Numerous intermediate-frequency, detectable regulatory polymorphisms cast doubt on a model in which cis-acting variation is a product of deleterious mutations of large effect. Comparing our data to predictions of population genetics theory using coalescent simulations, we estimate that a typical gene harbors 7–15 cis-regulatory sites (nucleotides) at which a selectively neutral mutation would elicit an observable expression phenotype. If standing cis-regulatory variation is actually slightly deleterious, the true mutational target size is larger.


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Genetics 2009 181: NP. [Full Text]