Change search
ReferencesLink to record
Permanent link

Direct link
Multidimensional epistasis and fitness landscapes in enzyme evolution
Show others and affiliations
2012 (English)In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 445, 39-46 p.Article in journal (Refereed) Published
Abstract [en]

The conventional analysis of enzyme evolution is to regard one single salient feature as a measure of fitness, expressed in a milieu exposing the possible selective advantage at a given time and location. Given that a single protein may serve more than one function, fitness should be assessed in several dimensions. In the present study we have explored individual mutational steps leading to a triple-point-mutated human GST (glutathione transferase) A2-2 displaying enhanced activity with azathioprine. A total of eight alternative substrates were used to monitor the diverse evolutionary trajectories. The epistatic effects of the imitations on catalytic activity were variable in sign and magnitude and depended on the substrate used, showing that epistasis is a multidimensional quality. Evidently, the multidimensional fitness landscape can lead to alternative trajectories resulting in enzymes optimized for features other than the selectable markers relevant at the origin of the evolutionary process. In this manner the evolutionary response is robust and can adapt to changing environmental conditions.

Place, publisher, year, edition, pages
2012. Vol. 445, 39-46 p.
Keyword [en]
epistasis, evolutionary trajectories, fitness landscape, multivariate data analysis, protein evolution, substrate selectivity
National Category
Other Medical Sciences Chemical Sciences
URN: urn:nbn:se:su:diva-81717DOI: 10.1042/BJ20120136ISI: 000306874300004OAI: diva2:563769


Available from: 2012-10-31 Created: 2012-10-30 Last updated: 2015-03-16Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Mannervik, Bengt
By organisation
Department of Neurochemistry
In the same journal
Biochemical Journal
Other Medical SciencesChemical Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 42 hits
ReferencesLink to record
Permanent link

Direct link