Evolvability as a function of purifying selection in TEM-1 β-lactamase.


Evolvability—the capacity to generate beneficial heritable variation—is a central property of biological systems. However, its origins and modulation by environmental factors have not been examined systematically. Here, we analyze the fitness effects of all single mutations in TEM-1 β-lactamase (4,997 variants) under selection for the wild-type function (ampicillin resistance) and for a new function (cefotaxime resistance). Tolerance to mutation in this enzyme is bimodal and dependent on the strength of purifying selection in vivo, a result that derives from a steep non-linear ampicillin-dependent relationship between biochemical activity and fitness. Interestingly, cefotaxime resistance emerges from mutations that are neutral at low levels of ampicillin but deleterious at high levels; thus the capacity to evolve new function also depends on the strength of selection. The key property controlling evolvability is an excess of enzymatic activity relative to the strength of selection, suggesting that fluctuating environments might select for high-activity enzymes.

Submission Details


Submitter: Shu-Ching Ou

Submission Date: July 24, 2018, 2:40 p.m.

Version: 1

Publication Details
Stiffler MA;Hekstra DR;Ranganathan R,Cell (2015) Evolvability as a function of purifying selection in TEM-1 β-lactamase. PMID:25723163
Additional Information

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