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Phenotypic constraints and phenotypic hitchhiking in a promiscuous enzyme


Wagner, Andreas; Weikert, Christian (2012). Phenotypic constraints and phenotypic hitchhiking in a promiscuous enzyme. Open Evolution Journal, 6:14-28.

Abstract

Covarying phenotypic traits can limit natural selection’s ability to modify these traits. Most evolutionary studies on trait covariation use the comparative method to study complex traits of multicellular organisms. Simpler traits have the advantage of being amenable to experimental evolution. Here we study such a simple molecular system, the TEM-1 beta-lactamase protein, a promiscuous enzyme that hydrolyses antibiotics, and thus confers antibiotic resistance to bacteria. We mutagenized large populations of TEM-1, and selected in these populations for activity on the four different antibiotics ampicillin, carbenicillin, oxacillin, and penicillin G. While mutagenesis alone lead to highly correlated changes in enzyme activity on the four antibiotics, subsequent selection was able to modify this activity covariation substantially, and even lead to uncorrelated activities. We found that selection on one antibiotic A may be more effective in increasing activity on another antibiotic B then selection on antibiotic B itself. We call this phenomenon phenotypic hitchhiking. It can be readily explained through quantitative genetic theory as a consequence of differing variances in covarying traits. It may help engineer macromolecules with desirable properties through directed evolution. Our analysis is a first step towards systematic analysis of trait covariation in experimental molecular systems. It shows that selection may readily modify the phenotypic constraints that limit its efficacy.

Abstract

Covarying phenotypic traits can limit natural selection’s ability to modify these traits. Most evolutionary studies on trait covariation use the comparative method to study complex traits of multicellular organisms. Simpler traits have the advantage of being amenable to experimental evolution. Here we study such a simple molecular system, the TEM-1 beta-lactamase protein, a promiscuous enzyme that hydrolyses antibiotics, and thus confers antibiotic resistance to bacteria. We mutagenized large populations of TEM-1, and selected in these populations for activity on the four different antibiotics ampicillin, carbenicillin, oxacillin, and penicillin G. While mutagenesis alone lead to highly correlated changes in enzyme activity on the four antibiotics, subsequent selection was able to modify this activity covariation substantially, and even lead to uncorrelated activities. We found that selection on one antibiotic A may be more effective in increasing activity on another antibiotic B then selection on antibiotic B itself. We call this phenomenon phenotypic hitchhiking. It can be readily explained through quantitative genetic theory as a consequence of differing variances in covarying traits. It may help engineer macromolecules with desirable properties through directed evolution. Our analysis is a first step towards systematic analysis of trait covariation in experimental molecular systems. It shows that selection may readily modify the phenotypic constraints that limit its efficacy.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Evolutionary Biology and Environmental Studies
Dewey Decimal Classification:570 Life sciences; biology
590 Animals (Zoology)
Language:English
Date:20 June 2012
Deposited On:07 Feb 2013 14:03
Last Modified:26 Jan 2017 08:53
Publisher:Bentham Open
ISSN:1874-4044
Publisher DOI:https://doi.org/10.2174/1874404401206010014

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