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The theory of facilitated variation
Open accessAbstract
This theory concerns the means by which animals generate phenotypic variation from genetic change. Most anatomical and physiological traits that have evolved since the Cambrian are, we propose, the result of regulatory changes in the usage of various members of a large set of conserved core components that function in development and physiology. Genetic change of the DNA sequences for regulatory elements of DNA, RNAs, and proteins leads to heritable regulatory change, which specifies new combinations of core components, operating in new amounts and states at new times and places in the animal. These new configurations of components comprise new traits. The number and kinds of regulatory changes needed for viable phenotypic variation are determined by the properties of the developmental and physiological processes in which core components serve, in particular by the processes' modularity, robustness, adaptability, capacity to engage in weak regulatory linkage, and exploratory behavior. These properties reduce the number of regulatory changes needed to generate viable selectable phenotypic variation, increase the variety of regulatory targets, reduce the lethality of genetic change, and increase the amount of genetic variation retained by a population. By such reductions and increases, the conserved core processes facilitate the generation of phenotypic variation, which selection thereafter converts to evolutionary and genetic change in the population. Thus, we call it a theory of facilitated phenotypic variation.
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The biology of VEGF and its receptors
Ferrara, N., Gerber, H.-P., & LeCouter, J. (2003) · Nature Medicine · doi:10.1038/nm0603-669 · Cited by 9,591
Initial sequencing and comparative analysis of the mouse genome
Mouse Genome Sequencing Consortium (2002) · Nature · doi:10.1038/nature01262 · Cited by 7,187
Developmental Plasticity and Evolution
West-Eberhard, M. J. (2003) · doi:10.1093/oso/9780195122343.001.0001 · Cited by 6,115
King, M.-C., & Wilson, A. C. (1975) · Science · doi:10.1126/science.1090005 · Cited by 2,815
Hsp90 as a capacitor for morphological evolution
Rutherford, S. L., & Lindquist, S. (1998) · Nature · doi:10.1038/24550 · Cited by 2,270
Baldwin, J. M. (1896) · The American Naturalist · doi:10.1086/276408 · Cited by 1,781
Transcription regulation and animal diversity
Levine, M., & Tjian, R. (2003) · Nature · doi:10.1038/nature01763 · Cited by 1,309
The calmodulin pathway and evolution of elongated beak morphology in Darwin's finches
Abzhanov, A., Kuo, W. P., Hartmann, C., Grant, B. R., Grant, P. R., & Tabin, C. J. (2006) · Nature · doi:10.1038/nature04843 · Cited by 636
Uncovering cryptic genetic variation
Gibson, G., & Dworkin, I. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1426 · Cited by 546
Bow ties, metabolism and disease
Csete, M., & Doyle, J. (2004) · Trends in biotechnology · doi:10.1016/j.tibtech.2004.07.007 · Cited by 468
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Tuning gene expression to changing environments: from rapid responses to evolutionary adaptation
López-Maury, L., Marguerat, S., & Bähler, J. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2398 · Cited by 1,061
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Prabakaran, S., Lippens, G., Steen, H., & Gunawardena, J. (2012) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1185 · Cited by 335
Levin, M. (2022) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2022.768201 · Cited by 195
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Bosco, D., Haefliger, J.-A., & Meda, P. (2011) · Physiological Reviews · doi:10.1152/physrev.00027.2010 · Cited by 169
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Norton, H. K., Emerson, D. J., Huang, H., Kim, J., Titus, K. R., Gu, S., Bassett, D. S., & Phillips-Cremins, J. E. (2018) · Nature Methods · doi:10.1038/nmeth.4560 · Cited by 146
Fields, C., & Levin, M. (2022) · Entropy · doi:10.3390/e24060819 · Cited by 121
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Suderman, R., & Deeds, E. J. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003278 · Cited by 52
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Hoke, K. L., Adkins-Regan, E., Bass, A. H., McCune, A. R., & Wolfner, M. F. (2019) · Journal of Experimental Biology · doi:10.1242/jeb.190058 · Cited by 42
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Matni, N., Ames, A. D., & Doyle, J. C. (2024) · IEEE Control Systems · doi:10.1109/mcs.2024.3382388 · Cited by 39
A modular circuit coordinates the diversification of courtship strategies
Coleman, R. T., Morantte, I., Koreman, G. T., Cheng, M. L., Ding, Y., & Ruta, V. (2024) · Nature · doi:10.1038/s41586-024-08028-1 · Cited by 32
Evolution and dispersal under climatic instability: a simple evolutionary algorithm
Grove, M. (2014) · Adaptive Behavior · doi:10.1177/1059712314533573 · Cited by 38
Martinez-Corral, R., Park, M., Biette, K. M., Friedrich, D., Scholes, C., Khalil, A. S., Gunawardena, J., & DePace, A. H. (2023) · Cell Systems · doi:10.1016/j.cels.2023.02.003 · Cited by 29
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Metadata
- Authors
- Gerhart, J., & Kirschner, M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2007-05-15
- Volume
- 104
- Issue
- suppl_1
- Pages
- 8582-8589
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2134735802
- Cited by
- 409
- References
- 11
- FWCI
- 7.87
- Type
- journal article
- Language
- en
- Open access
- green
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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.
