Multidimensional epistasis and fitness landscapes in enzyme evolution

• Tipo: Artigo em Revista Científica Internacional
• Data: 2012

Autores

Wei Zhang (Autor) Outra; Daniel F A R Dourado (Autor) Outra; Pedro Alexandrino Fernandes (Autor) FCUP; Maria Joao Ramos (Autor) FCUP; Bengt Mannervik (Autor) Outra

Revista

Título: Biochemical Journal

Vol. 445

Páginas: 39-46

ISSN: 0264-6021

Editora: PORTLAND PRESS LTD

Indexação

ISI Web of Knowledge - 21 Citações

Scopus - 25 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Ciências biológicas

Outras Informações

ID Authenticus: P-002-89M

DOI: 10.1042/bj20120136

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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 8