Saturating the eQTL map in Drosophila melanogaster: genome-wide patterns of cis and trans regulation of transcriptional variation in outbred populations

Decades of genome-wide mapping have shown that most genetic polymorphisms associated with complex traits are found in non-coding regions of the genome. Characterizing the effect of such genetic variation presents a formidable challenge, and eQTL mapping has been a key approach to understand the non-coding genome. However, comprehensive eQTL maps are available only for a few species like yeast and humans. With the aim of understanding the genetic landscape that regulates transcriptional variation in Drosophila melanogaster, we developed an outbred mapping panel in this species, the Drosophila Outbred Synthetic Panel (Dros-OSP). Using this community resource, we collected transcriptomic and genomic data for 1800 individual flies and were able to map cis and trans eQTLs for 98% of the genes expressed in D. melanogaster, increasing by thousands the number of genes for which regulatory loci are known in this species. We described, for the first time in the context of an outbred population, the properties of local and distal regulation of gene expression in terms of genetic diversity, heritability, connectivity, and pleiotropy. We uncovered that, contrary to long-standing assumptions, a significant part of gene co-expression networks is organized in a non-modular fashion. These results bring the fruit fly to the level of understanding that was only available for a few other organisms, and offer a new mapping resource that will expand the possibilities currently available to the Drosophila community. This data is available at Drosophilaeqtl.org.