The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
A Comprehensive, High-Resolution Map of a Gene’s Fitness Landscape
Open accessAbstract
Mutations are central to evolution, providing the genetic variation upon which selection acts. A mutation's effect on the suitability of a gene to perform a particular function (gene fitness) can be positive, negative, or neutral. Knowledge of the distribution of fitness effects (DFE) of mutations is fundamental for understanding evolutionary dynamics, molecular-level genetic variation, complex genetic disease, the accumulation of deleterious mutations, and the molecular clock. We present comprehensive DFEs for point and codon mutants of the Escherichia coli TEM-1 β-lactamase gene and missense mutations in the TEM-1 protein. These DFEs provide insight into the inherent benefits of the genetic code's architecture, support for the hypothesis that mRNA stability dictates codon usage at the beginning of genes, an extensive framework for understanding protein mutational tolerance, and evidence that mutational effects on protein thermodynamic stability shape the DFE. Contrary to prevailing expectations, we find that deleterious effects of mutation primarily arise from a decrease in specific protein activity and not cellular protein levels.
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Cites
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The distribution of fitness effects caused by single-nucleotide substitutions in an RNA virus.
Sanjuán, R., Moya, A., & Elena, S. F. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400146101 · Cited by 582
Causes and effects of N-terminal codon bias in bacterial genes
Goodman, D. B., Church, G. M., & Kosuri, S. (2013) · Science · doi:10.1126/science.1241934 · Cited by 573
On the evolution of the genetic code.
Woese, C. R. (1965) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.54.6.1546 · Cited by 487
Robustness–epistasis link shapes the fitness landscape of a randomly drifting protein
Bershtein, S., Segal, M., Bekerman, R., Tokuriki, N., & Tawfik, D. S. (2006) · Nature · doi:10.1038/nature05385 · Cited by 414 · cited 13×
“Previous partial characterizations of the DFE of TEM-1 (Bershtein et al. 2006; Deng et al. 2012; Jacquier et al. 2013) suffer several significant limitations.”
BackgroundMethodInfluentialAraya, C. L., Fowler, D. M., Chen, W., Muniez, I., Kelly, J. W., & Fields, S. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209751109 · Cited by 230
The genetic code constrains yet facilitates Darwinian evolution
Firnberg, E., & Ostermeier, M. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt536 · Cited by 36
Self-citation
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Mutation effects predicted from sequence co-variation
Hopf, T. A., Ingraham, J. B., Poelwijk, F. J., Schärfe, C. P. I., Springer, M., Sander, C., & Marks, D. S. (2017) · Nature Biotechnology · doi:10.1038/nbt.3769 · Cited by 775
Language models enable zero-shot prediction of the effects of mutations on protein function
Meier, J., Rao, R., Verkuil, R., Liu, J., Sercu, T., & Rives, A. (2021) · doi:10.1101/2021.07.09.450648 · Cited by 635
Deep generative models of genetic variation capture the effects of mutations
Riesselman, A. J., Ingraham, J. B., & Marks, D. S. (2018) · Nature Methods · doi:10.1038/s41592-018-0138-4 · Cited by 601
Local fitness landscape of the green fluorescent protein
Sarkisyan, K. S., Bolotin, D. A., Meer, M. V., Usmanova, D. R., Mishin, A. S., Sharonov, G. V., Ivankov, D. N., Bozhanova, N. G., Baranov, M. S., Soylemez, O., et al. (2016) · Nature · doi:10.1038/nature17995 · Cited by 591
Sequence modeling and design from molecular to genome scale with Evo
Nguyen, E., Poli, M., Durrant, M. G., Kang, B., Katrekar, D., Li, D. B., Bartie, L. J., Thomas, A. W., King, S. H., Brixi, G., et al. (2024) · Science · doi:10.1126/science.ado9336 · Cited by 580
Metadata
- Authors
- Firnberg, E., Labonte, J. W., Gray, J. J., & Ostermeier, M.
- Venue
- Molecular Biology and Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-02-23
- Volume
- 31
- Issue
- 6
- Pages
- 1581-1592
- ISSN
- 0737-4038 (ISSN-L)
- 1537-1719
- OpenAlex
- W2144893575
- Cited by
- 337
- References
- 7
- FWCI
- 15.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
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