Regulatory changes underlying expression differences within and between Drosophila species (original) (raw)
- Letter
- Published: 17 February 2008
Nature Genetics volume 40, pages 346–350 (2008)Cite this article
- 3268 Accesses
- 293 Citations
- 12 Altmetric
- Metrics details
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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Additional access options:
Similar content being viewed by others
References
- Yvert, G. et al. Trans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors. Nat. Genet. 35, 57–64 (2003).
Article CAS Google Scholar - Wittkopp, P.J., Haerum, B.K. & Clark, A.G. Evolutionary changes in cis and trans gene regulation. Nature 430, 85–88 (2004).
Article CAS Google Scholar - West, M. et al. Global eQTL mapping reveals the complex genetic architecture of transcript-level variation in Arabidopsis. Genetics 175, 1441–1450 (2007).
Article CAS Google Scholar - Schadt, E.E. et al. Genetics of gene expression surveyed in maize, mouse and man. Nature 422, 297–302 (2003).
Article CAS Google Scholar - Morley, M. et al. Genetic analysis of genome-wide variation in human gene expression. Nature 430, 743–747 (2004).
Article CAS Google Scholar - Li, Y. et al. Mapping determinants of gene expression plasticity by genetical genomics in C. elegans. PLoS Genet. 2, e222 (2006).
Article Google Scholar - Brem, R.B., Yvert, G., Clinton, R. & Kruglyak, L. Genetic dissection of transcriptional regulation in budding yeast. Science 296, 752–755 (2002).
Article CAS Google Scholar - Gibson, G. et al. Extensive sex-specific nonadditivity of gene expression in Drosophila melanogaster. Genetics 167, 1791–1799 (2004).
Article CAS Google Scholar - Meiklejohn, C.D., Parsch, J., Ranz, J.M. & Hartl, D.L. Rapid evolution of male-biased gene expression in Drosophila. Proc. Natl. Acad. Sci. USA 100, 9894–9899 (2003).
Article CAS Google Scholar - Michalak, P. & Noor, M.A. Genome-wide patterns of expression in Drosophila pure species and hybrid males. Mol. Biol. Evol. 20, 1070–1076 (2003).
Article CAS Google Scholar - Ranz, J.M., Castillo-Davis, C.I., Meiklejohn, C.D. & Hartl, D.L. Sex-dependent gene expression and evolution of the Drosophila transcriptome. Science 300, 1742–1745 (2003).
Article CAS Google Scholar - Rifkin, S.A., Kim, J. & White, K.P. Evolution of gene expression in the Drosophila melanogaster subgroup. Nat. Genet. 33, 138–144 (2003).
Article CAS Google Scholar - Powell, J.R. Progress and Prospects in Evolutionary Biology: the Drosophila Model (Oxford Univ. Press, New York, 1997).
Google Scholar - Ranz, J.M., Namgyal, K., Gibson, G. & Hartl, D.L. Anomalies in the expression profile of interspecific hybrids of Drosophila melanogaster and Drosophila simulans. Genome Res. 14, 373–379 (2004).
Article CAS Google Scholar - Wittkopp, P.J., Haerum, B.K. & Clark, A.G. Parent-of-origin effects on mRNA expression in Drosophila melanogaster not caused by genomic imprinting. Genetics 173, 1817–1821 (2006).
Article CAS Google Scholar - Landry, C.R. et al. Compensatory cis-trans evolution and the dysregulation of gene expression in interspecific hybrids of Drosophila. Genetics 171, 1813–1822 (2005).
Article CAS Google Scholar - Storey, J.D. & Tibshirani, R. Statistical significance for genomewide studies. Proc. Natl. Acad. Sci. USA 100, 9440–9445 (2003).
Article CAS Google Scholar - Osada, N., Kohn, M.H. & Wu, C.I. Genomic inferences of the _cis_-regulatory nucleotide polymorphisms underlying gene expression differences between Drosophila melanogaster mating races. Mol. Biol. Evol. 23, 1585–1591 (2006).
Article CAS Google Scholar - McDonald, J.H. & Kreitman, M. Adaptive protein evolution at the Adh locus in Drosophila. Nature 351, 652–654 (1991).
Article CAS Google Scholar - Wittkopp, P.J. Genomic sources of regulatory variation in cis and in trans. Cell. Mol. Life Sci. 62, 1779–1783 (2005).
Article CAS Google Scholar - Landry, C.R., Lemos, B., Rifkin, S.A., Dickinson, W.J. & Hartl, D.L. Genetic properties influencing the evolvability of gene expression. Science 317, 118–121 (2007).
Article CAS Google Scholar - Denver, D.R. et al. The transcriptional consequences of mutation and natural selection in Caenorhabditis elegans. Nat. Genet. 37, 544–548 (2005).
Article CAS Google Scholar - Wray, G. The evolutionary significance of _cis_-regulatory mutations. Nat. Rev. Genet. 8, 206–216 (2007).
Article CAS Google Scholar - Akritas, M. & Bershady, M. Linear regression for astronomical data with measurement errors and intrinsic scatter. Astrophys. J. 470, 706–714 (1996).
Article Google Scholar
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.
Author information
Authors and Affiliations
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, 14853, New York, USA
Patricia J Wittkopp, Belinda K Haerum & Andrew G Clark - 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
- Patricia J Wittkopp
You can also search for this author inPubMed Google Scholar - Belinda K Haerum
You can also search for this author inPubMed Google Scholar - Andrew G Clark
You can also search for this author inPubMed Google Scholar
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.
Corresponding author
Correspondence toPatricia J Wittkopp.
Supplementary information
Rights and permissions
About this article
Cite this article
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
- Received: 15 June 2007
- Accepted: 11 December 2007
- Published: 17 February 2008
- Issue Date: March 2008
- DOI: https://doi.org/10.1038/ng.77