Allele-specific expression analysis in a large panel of intraspecific Drosophila melanogaster crosses. Daniel Campo¹, Justin Fear², Rita Graze², Peter Poon¹, Matt Salomon¹, John Tower¹, Lauren McIntyre², Sergey Nuzhdin¹. 1) University of Southern California, Los Angeles, CA; 2) University of Florida, Gainesville, FL.

   Gene expression variation is an important source of phenotypic change and therefore it has important implications for small-scale evolutionary processes, like local adaptation, population differentiation, and speciation. Thus, understanding how gene expression is regulated at the genome level can shed light on how these processes shape phenotypic diversity. Here we investigate the contribution of cis- and trans- regulatory changes to allele-specific expression (ASE) differences in intraspecific hybrids of Drosophila melanogaster. We have re-sequenced the entire transcriptome of a panel of 115 F1 heterozygous genotypes, derived from a set of crosses between 115 isogenic lines (N Raleigh Drosophila reference panel lines plus N Winters lines) and the isogenized standard strain w[1118]. Whole genome sequences for all the parental isogenic lines are available. For each F1 genotype, we estimated ASE using a mixed-effects model that accounts for differences between technical replicates. In each case, the p-value was adjusted for a False Discovery Rate (FDR) that takes into account all genotypes analyzed. We found significant ASE for the majority of genes. This amount of cis- regulatory divergence appears surprisingly high at first glance. However, previous studies focused on one or a few genotypes, and cis-regulation needs to be polymorphic to be revealed. In our large collection of genotypes, we are able to more effectively uncover cis-variation for the gene. The vast amount of cis-variation suggests that much of the adaptive evolution at the population level might be due to variation in gene expression rather than changes at the protein level.Additionally, because we used the common parental fly line w[1118] in all the crosses, we will be also able to identify the relative contribution of trans- regulatory changes. These differences in allelic expression will be further associated with specific polymorphisms at the nucleotide level.