title: Cis-regulatory variation is typically polyallelic in Drosophila.
abstract: Gene expression levels vary heritably, with approximately 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.
authors.affiliation: Ecology and Evolutionary Biology, University of California, Irvine, California 92697, USA. gruberjd@umich.edu
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Gruber
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Long
mesh_terms: D000483:Alleles; D000818:Animals; D000835:Animals, Wild / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D017344:Genes, Insect; D005816:Genetic Complementation Test; D014644:Genetic Variation; D005828:Genetics, Population; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide