Pervasive tissue-, genetic background-, and allele-specific gene expression effects in Drosophila melanogaster

Abstract

The pervasiveness of gene expression variation and its contribution to phenotypic variation and evolution is well known. This gene expression variation is context dependent, with differences in regulatory architecture often associated with intrinsic and environmental factors, and is modulated by regulatory elements that can act in cis (linked) or in trans (unlinked) relative to the genes they affect. So far, little is known about how this genetic variation affects the evolution of regulatory architecture among closely related tissues during population divergence. To address this question, we analyzed gene expression in the midgut, hindgut, and Malpighian tubule as well as microbiome composition in the two gut tissues in four Drosophila melanogaster strains and their F1 hybrids from two divergent populations: one from the derived, European range and one from the ancestral, African range. In both the transcriptome and microbiome data, we detected extensive tissue- and genetic background-specific effects, including effects of genetic background on overall tissue specificity. Tissue-specific effects were typically stronger than genetic background-specific effects, although the two gut tissues were not more similar to each other than to the Malpighian tubules. An examination of allele specific expression revealed that, while both cis and trans effects were more tissue-specific in genes expressed differentially between populations than genes with conserved expression, trans effects were more tissue-specific than cis effects. Despite there being highly variable regulatory architecture, this observation was robust across tissues and genetic backgrounds, suggesting that the expression of trans variation can be spatially fine-tuned as well as or better than cis variation during population divergence and yielding new insights into cis and trans regulatory evolution. Author SummaryGenetic variants regulating gene expression can act in cis (linked) or in trans (unlinked) relative to the genes they affect and are thought to be important during adaptation because they can spatially and temporally fine-tune gene expression. In this study, we used the fruit fly Drosophila melanogaster to compare gene expression between inbred parental strains and their offspring in order to characterize the basis of gene expression regulation and inheritance. We examined gene expression in three tissues (midgut, hindgut, and Malpighian tubule) and four genetic backgrounds stemming from Europe and the ancestral range in Africa. Additionally, we characterized the bacterial community composition in the two gut tissues. We detected extensive tissue- and genetic background-specific effects on gene expression and bacterial community composition, although tissue-specific effects were typically stronger than genetic background effects. Genes with cis and trans regulatory effects were more tissue-specific than genes with conserved expression, while those with trans effects were more tissue-specific than those with cis effects. These results suggest that the expression of trans variation can be spatially fine-tuned as well as (or better than) cis variation as populations diverge from one another. Our study yields novel insight into the genetic basis of gene regulatory evolution.