A comprehensive, high-resolution map of a gene's fitness landscape.


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.

Submission Details

ID: 9qCh9wU7

Submitter: Shu-Ching Ou

Submission Date: July 23, 2018, 8:51 p.m.

Version: 1

Publication Details
Firnberg E;Labonte JW;Gray JJ;Ostermeier M,Mol Biol Evol (2014) A comprehensive, high-resolution map of a gene's fitness landscape. PMID:24567513
Additional Information

Study Summary

Number of data points 10938
Proteins Beta-lactamase TEM
Unique complexes 5199
Assays/Quantities/Protocols Experimental Assay: Mutational Tolerance
Libraries Protein fitness values for ampicillin resistance

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Beta-lactamase TEM P62593 BLAT_ECOLX
100.0 Beta-lactamase TEM P62594 BLAT_SALTI
99.7 Beta-lactamase TEM Q48406 BLAT_KLEOX