Abstract
Differences in gene expression are an important source of phenotypic variation, and can be caused by changes in cis and/or trans regulation. cis-regulatory variants alter allele-specific expression, whereas trans-regulatory variants influence expression of both alleles in a diploid cell. Because of this difference, we hypothesize that natural selection may favor one type of change over the other. Here, we investigate contributions of cis- and trans-regulatory changes to variable intra- and interspecific gene expression using four strains of Drosophila melanogaster, three strains of D. simulans and a total of 78 genes. We show that cis-regulatory changes account for a greater proportion of the expression differences observed between rather than within species. These data are inconsistent with a neutral model assuming equal probabilities of fixation for cis- and trans-regulatory polymorphisms, suggesting that natural selection influences the molecular mechanisms underlying divergent gene expression. Specifically, cis-regulatory changes seem to accumulate preferentially over time.
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Acknowledgements
We thank R. Haygood, K. Montooth, H.A. Orr, B. Payseur, D. Presgraves, G. Wray and anonymous reviewers for helpful discussions of this work. We thank D. Barbash, H. Hollocher, C. Landry, S. Nuzhdin and H.A. Orr for sharing fly strains, and K. Montooth, J. Zhang, B. Payseur, and G. Kalay for comments on the manuscript. Funding for this project was provided by US National Institutes of Health grants to A.G.C. P.J.W. was a Damon Runyon Fellow supported by the Damon Runyon Cancer Research Foundation, and B.K.H. was funded by a Howard Hughes Undergraduate Research award.
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P.J.W. conceived and designed the experiments. B.K.H. and P.J.W. performed fly crosses and collected the allelic expression data. P.J.W. performed statistical analyses and prepared the manuscript in consultation with A.G.C., who also provided reagents and other resources for the project.
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Supplementary Text and Figures
Supplementary Methods, Supplementary Note, Supplementary Figures 1–4, Supplementary Tables 1, 4 and 5 (PDF 1109 kb)
Supplementary Table 2
Genes analyzed (XLS 36 kb)
Supplementary Table 3
Summary of LS means and statistical tests (XLS 2226 kb)
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Wittkopp, P., Haerum, B. & Clark, A. Regulatory changes underlying expression differences within and between Drosophila species. Nat Genet 40, 346–350 (2008). https://doi.org/10.1038/ng.77
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DOI: https://doi.org/10.1038/ng.77
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