The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
The Evolution of Transcriptional Regulation in Eukaryotes
Open accessAbstract
Gene expression is central to the genotype-phenotype relationship in all organisms, and it is an important component of the genetic basis for evolutionary change in diverse aspects of phenotype. However, the evolution of transcriptional regulation remains understudied and poorly understood. Here we review the evolutionary dynamics of promoter, or cis-regulatory, sequences and the evolutionary mechanisms that shape them. Existing evidence indicates that populations harbor extensive genetic variation in promoter sequences, that a substantial fraction of this variation has consequences for both biochemical and organismal phenotype, and that some of this functional variation is sorted by selection. As with protein-coding sequences, rates and patterns of promoter sequence evolution differ considerably among loci and among clades for reasons that are not well understood. Studying the evolution of transcriptional regulation poses empirical and conceptual challenges beyond those typically encountered in analyses of coding sequence evolution: promoter organization is much less regular than that of coding sequences, and sequences required for the transcription of each locus reside at multiple other loci in the genome. Because of the strong context-dependence of transcriptional regulation, sequence inspection alone provides limited information about promoter function. Understanding the functional consequences of sequence differences among promoters generally requires biochemical and in vivo functional assays. Despite these challenges, important insights have already been gained into the evolution of transcriptional regulation, and the pace of discovery is accelerating.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The genetical theory of natural selection
Fisher, R. A. (1930) · doi:10.5962/bhl.title.27468 · Cited by 17,617
The sequence of the human genome
Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith, H. O., Yandell, M., Evans, C. A., Holt, R. A., et al. (2001) · Science · doi:10.1126/science.1058040 · Cited by 13,909
Network motifs: simple building blocks of complex networks.
Milo, R., Shen-Orr, S., Itzkovitz, S., Kashtan, N., Chklovskii, D., & Alon, U. (2002) · Science · doi:10.1126/science.298.5594.824 · Cited by 7,368
Initial sequencing and comparative analysis of the mouse genome
Mouse Genome Sequencing Consortium (2002) · Nature · doi:10.1038/nature01262 · Cited by 7,187
Transcriptional Regulatory Networks in Saccharomyces cerevisiae
Lee, T. I., Rinaldi, N. J., Robert, F., Odom, D. T., Bar-Joseph, Z., Gerber, G. K., Hannett, N. M., Harbison, C. T., Thompson, C. M., Simon, I., et al. (2002) · Science · doi:10.1126/science.1075090 · Cited by 2,956
King, M.-C., & Wilson, A. C. (1975) · Science · doi:10.1126/science.1090005 · Cited by 2,815
Serotonin transporter genetic variation and the response of the human amygdala.
Hariri, A. R., Mattay, V. S., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., Egan, M. F., & Weinberger, D. R. (2002) · Science · doi:10.1126/science.1071829 · Cited by 2,340
The segment polarity network is a robust developmental module
von Dassow, G., Meir, E., Munro, E. M., & Odell, G. M. (2000) · Nature · doi:10.1038/35018085 · Cited by 1,144
Homology of the eyeless Gene of Drosophila to the Small eye Gene in Mice and Aniridia in Humans
Quiring, R., Walldorf, U., Kloter, U., & Gehring, W. J. (1994) · Science · doi:10.1126/science.7914031 · Cited by 1,100
Pax 6: mastering eye morphogenesis and eye evolution
Gehring, W. J., & Ikeo, K. (1999) · Trends in Genetics · doi:10.1016/s0168-9525(99)01776-x · Cited by 758
Cited by
Evolution of Gene Duplication in Plants
Panchy, N., Lehti-Shiu, M., & Shiu, S.-H. (2016) · Plant Physiology · doi:10.1104/pp.16.00523 · Cited by 1,757
Convergent adaptation of human lactase persistence in Africa and Europe
Tishkoff, S. A., Reed, F. A., Ranciaro, A., Voight, B. F., Babbitt, C. C., Silverman, J. S., Powell, K., Mortensen, H. M., Hirbo, J. B., Osman, M., et al. (2007) · Nature Genetics · doi:10.1038/ng1946 · Cited by 1,615
Self-citationThe evolution of gene regulation by transcription factors and microRNAs
Chen, K., & Rajewsky, N. (2007) · Nature Reviews Genetics · doi:10.1038/nrg1990 · Cited by 1,547
The evolutionary significance of cis-regulatory mutations
Wray, G. A. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2063 · Cited by 1,521
Self-citationGene regulation by transcription factors and microRNAs
Hobert, O. (2008) · Science · doi:10.1126/science.1151651 · Cited by 913
Finding the genomic basis of local adaptation: pitfalls, practical solutions, and future directions
Hoban, S., Kelley, J. L., Lotterhos, K. E., Antolin, M. F., Bradburd, G., Lowry, D. B., Poss, M. L., Reed, L. K., Storfer, A., & Whitlock, M. C. (2016) · The American Naturalist · doi:10.1086/688018 · Cited by 876
“…regulatory and coding regions, these meth-ods may fail to capture variation involved in gene regulation — such as enhancers and copy number variation — that may underlie the majority of adaptive phenotypic variation (Wray et al. 2003; Perry et al. 2007; Rockman 2012; Stern and Orgogozo 2008).”
Evolutionary changes in cis and trans gene regulation
Wittkopp, P. J., Haerum, B. K., & Clark, A. G. (2004) · Nature · doi:10.1038/nature02698 · Cited by 873
Long-Range Control of Gene Expression: Emerging Mechanisms and Disruption in Disease
Kleinjan, D. A., & van Heyningen, V. (2005) · The American Journal of Human Genetics · doi:10.1086/426833 · Cited by 873
Global Analysis of Cdk1 Substrate Phosphorylation Sites Provides Insights into Evolution
Holt, L. J., Tuch, B. B., Villén, J., Johnson, A. D., Gygi, S. P., & Morgan, D. O. (2009) · Science · doi:10.1126/science.1172867 · Cited by 869
The frailty of adaptive hypotheses for the origins of organismal complexity
Lynch, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702207104 · Cited by 817
Genetics of global gene expression
Rockman, M. V., & Kruglyak, L. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1964 · Cited by 666
Microsatellite instability generates diversity in brain and sociobehavioral traits
Hammock, E. A. D., & Young, L. J. (2005) · Science · doi:10.1126/science.1111427 · Cited by 545
High-Resolution Mapping of Expression-QTLs Yields Insight into Human Gene Regulation
Veyrieras, J.-B., Kudaravalli, S., Kim, S. Y., Dermitzakis, E. T., Gilad, Y., Stephens, M., & Pritchard, J. K. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000214 · Cited by 536
The deep evolution of metazoan microRNAs
Wheeler, B. M., Heimberg, A. M., Moy, V. N., Sperling, E. A., Holstein, T. W., Heber, S., & Peterson, K. J. (2009) · Evolution & Development · doi:10.1111/j.1525-142x.2008.00302.x · Cited by 534
Role of Secondary Metabolites and Brassinosteroids in Plant Defense Against Environmental Stresses
Bartwal, A., Mall, R., Lohani, P., Guru, S. K., & Arora, S. (2013) · Journal of Plant Growth Regulation · doi:10.1007/s00344-012-9272-x · Cited by 494
The evolution of hierarchical gene regulatory networks
Erwin, D. H., & Davidson, E. H. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2499 · Cited by 454
Whole-Genome Analysis of the SHORT-ROOT Developmental Pathway in Arabidopsis
Levesque, M. P., Vernoux, T., Busch, W., Cui, H., Wang, J. Y., Blilou, I., Hassan, H., Nakajima, K., Matsumoto, N., Lohmann, J. U., et al. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040143 · Cited by 349
Comparing the human and chimpanzee genomes: Searching for needles in a haystack
Varki, A., & Altheide, T. K. (2005) · Genome Research · doi:10.1101/gr.3737405 · Cited by 344
Duarte, J. M., Cui, L., Wall, P. K., Zhang, Q., Zhang, X., Leebens-Mack, J., Ma, H., Altman, N., & dePamphilis, C. W. (2006) · Molecular Biology and Evolution · doi:10.1093/molbev/msj051 · Cited by 339
Endogenous retroviral LTRs as promoters for human genes: A critical assessment
Cohen, C. J., Lock, W. M., & Mager, D. L. (2009) · Gene · doi:10.1016/j.gene.2009.06.020 · Cited by 314
Genetics and epigenetics: stability and plasticity during cellular differentiation
Mohn, F., & Schübeler, D. (2009) · Trends in Genetics · doi:10.1016/j.tig.2008.12.005 · Cited by 301
The evolution of phenylpropanoid metabolism in the green lineage
Tohge, T., Watanabe, M., Hoefgen, R., & Fernie, A. R. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2012.758083 · Cited by 296
Epigenetic responses to environmental change and their evolutionary implications
Turner, B. M. (2009) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2009.0125 · Cited by 293
Evolutionary constraint and innovation across hundreds of placental mammals
Christmas, M. J., Kaplow, I. M., Genereux, D. P., Dong, M. X., Hughes, G. M., Li, X., Sullivan, P. F., Hindle, A. G., Andrews, G., Armstrong, J. C., et al. (2023) · Science · doi:10.1126/science.abn3943 · Cited by 292
Chang, W.-C., Lee, T.-Y., Huang, H.-D., Huang, H.-Y., & Pan, R.-L. (2008) · BMC Genomics · doi:10.1186/1471-2164-9-561 · Cited by 289
Networks of transcription factors with roles in environmental stress response
Chen, W. J., & Zhu, T. (2004) · Trends in Plant Science · doi:10.1016/j.tplants.2004.10.007 · Cited by 288
Molecular and evolutionary processes generating variation in gene expression
Hill, M. S., Vande Zande, P., & Wittkopp, P. J. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-020-00304-w · Cited by 266
Regulatory polymorphisms underlying complex disease traits.
Knight, J. C. (2005) · Journal of Molecular Medicine · doi:10.1007/s00109-004-0603-7 · Cited by 246
Acquisition of aluminium tolerance by modification of a single gene in barley
Fujii, M., Yokosho, K., Yamaji, N., Saisho, D., Yamane, M., Takahashi, H., Sato, K., Nakazono, M., & Ma, J. F. (2012) · Nature Communications · doi:10.1038/ncomms1726 · Cited by 197
Moses, A. M., Chiang, D. Y., Pollard, D. A., Iyer, V. N., & Eisen, M. B. (2004) · Genome Biology · doi:10.1186/gb-2004-5-12-r98 · Cited by 153
Intersecting transcription networks constrain gene regulatory evolution
Sorrells, T. R., Booth, L. N., Tuch, B. B., & Johnson, A. D. (2015) · Nature · doi:10.1038/nature14613 · Cited by 69
Balhoff, J. P., & Wray, G. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409638102 · Cited by 69
Self-citationTranscription factor binding variation in the evolution of gene regulation
Dowell, R. D. (2010) · Trends in Genetics · doi:10.1016/j.tig.2010.08.005 · Cited by 61
Extreme context specificity in differential allelic expression
Wilkins, J. M., Southam, L., Price, A. J., Mustafa, Z., Carr, A., & Loughlin, J. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddl488 · Cited by 53
Quantitative measurement of allele‐specific protein expression in a diploid yeast hybrid by LC‐MS
Khan, Z., Bloom, J. S., Amini, S., Singh, M., Perlman, D. H., Caudy, A. A., & Kruglyak, L. (2012) · Molecular Systems Biology · doi:10.1038/msb.2012.34 · Cited by 37
The mouth, the anus, and the blastopore—open questions about questionable openings
Hejnol, A., & Martindale, M. Q. (2009) · Animal Evolution · doi:10.1093/acprof:oso/9780199549429.003.0004 · Cited by 37
Muntané, G., Horvath, J. E., Hof, P. R., Ely, J. J., Hopkins, W. D., Raghanti, M. A., Lewandowski, A. H., Wray, G. A., & Sherwood, C. C. (2015) · Cerebral Cortex · doi:10.1093/cercor/bht354 · Cited by 36
Self-citationDivergent and nonuniform gene expression patterns in mouse brain
Morris, J. A., Royall, J. J., Bertagnolli, D., Boe, A. F., Burnell, J. J., Byrnes, E. J., Copeland, C., Desta, T., Fischer, S. R., Goldy, J., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003732107 · Cited by 36
Genomic, phylogenetic, and cell biological insights into metazoan origins
Nichols, S. A., Dayel, M. J., & King, N. (2009) · Animal Evolution · doi:10.1093/acprof:oso/9780199549429.003.0003 · Cited by 24
Human genetic variation within neural crest enhancers: molecular and phenotypic implications
Rada-Iglesias, A., Prescott, S. L., & Wysocka, J. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2012.0360 · Cited by 24
Theobald, D. L. (2011) · Biology Direct · doi:10.1186/1745-6150-6-60 · Cited by 16
“Similarly, one can align promoter sequences to find common motifs, without assuming that the promoters actually originated by descent from a common ancestral sequence [113].”
BackgroundComprehensive Nanorobotic Control of Human Morbidity and Aging
Freitas, R. A. (2010) · The Future of Aging · doi:10.1007/978-90-481-3999-6_23 · Cited by 16
Extensive Changes in the Expression of the Opioid Genes between Humans and Chimpanzees
Cruz-Gordillo, P., Fedrigo, O., Wray, G. A., & Babbitt, C. C. (2010) · Brain, Behavior and Evolution · doi:10.1159/000320968 · Cited by 16
Self-citationCauTrigger: deciphering biological system state transitions by hierarchical causal decomposition
Zhang, C., Cai, D., Aihara, K., & Chen, L. (2026) · Nature Methods · doi:10.1038/s41592-026-03274-9
Metadata
- Authors
- Wray, G. A.
- Venue
- Molecular Biology and Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-05-30
- Volume
- 20
- Issue
- 9
- Pages
- 1377-1419
- ISSN
- 0737-4038 (ISSN-L)
- 1537-1719
- OpenAlex
- W2133147430
- Cited by
- 1,222
- References
- 21
- FWCI
- 35.00
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.