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Changes in host specialization contribute to the diversification of phytophagous insects. When shifting to a new host, insects evolve new physiological, morphological, and behavioral adaptations. Our understanding of the genetic changes responsible for these adaptations is limited. For instance, we do not know how often host shifts involve gain-of-function vs. loss-of-function alleles. Recent work suggests that some genes involved in odor recognition are lost in specialists. Here we show that genes involved in detoxification and metabolism, as well as those affecting olfaction, have reduced gene expression in Drosophila sechellia—a specialist on the fruit of Morinda citrifolia. We screened for genes that differ in expression between D. sechellia and its generalist sister species, D. simulans. We also screened for genes that are differentially expressed in D. sechellia when these flies chose their preferred host vs …