Massive habitat-specific genomic response in D. melanogaster populations during experimental evolution in hot and...

Experimental evolution in combination with whole-genome sequencing (evolve and resequence [E&R]) is a promising approach to define the genotype-phenotype map and to understand adaptation in evolving populations. Many previous studies have identified a large number of putative selected sites (i.e., candidate loci), but it remains unclear to what extent these loci are genuine targets of selection or experimental noise. To address this question, we exposed the same founder population to two different selection regimes-a hot environment and a cold environment-and quantified the genomic response in each. We detected large numbers of putative selected loci in both environments, albeit with little overlap between the two sets of candidates, indicating that most resulted from habitat-specific selection. By quantifying changes across multiple independent biological replicates, we demonstrate that most of the candidate SNPs were false positives that were linked to selected sites over distances much larger than the typical linkage disequilibrium range of Drosophila melanogaster. We show that many of these mid- to long-range associations were attributable to large segregating inversions and confirm by computer simulations that such patterns could be readily replicated when strong selection acts on rare haplotypes. In light of our findings, we outline recommendations to improve the performance of future Drosophila E&R studies which include using species with negligible inversion loads, such as D. mauritiana and D. simulans, instead of D. melanogaster.