Regulatory changes underlying expression differences within and between Drosophila species (original) (raw)

Nature Genetics volume 40, pages 346–350 (2008)Cite this article

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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Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Cornell University, Ithaca, 14853, New York, USA
    Patricia J Wittkopp, Belinda K Haerum & Andrew G Clark
  2. Department of Ecology and Evolutionary Biology, Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, 48109, Michigan, USA
    Patricia J Wittkopp & Belinda K Haerum

Authors

  1. Patricia J Wittkopp
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  2. Belinda K Haerum
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  3. Andrew G Clark
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Contributions

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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Correspondence toPatricia J Wittkopp.

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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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