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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A Comprehensive Biophysical Description of Pairwise Epistasis throughout an Entire Protein Domain
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Origins and breadth of pairwise epistasis in an α-helix of β-lactamase TEM-1
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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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