Molecular evolution and the role of oxidative stress in the expansion and functional diversification of cytosolic glutathione transferases

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Rute R da Fonseca (Author) Other; Warren E Johnson (Author) Other; Stephen J O'Brien (Author) Other; Vitor Vasconcelos (Author) FCUP; Agostinho Antunes (Author) FCUP

Journal

Title: BMC Evolutionary Biology

Vol. 10

Final page: 281

ISSN: 1471-2148

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 62 Citations

Scopus - 64 Citations

Scientific classification

FOS: Natural sciences > Earth and related Environmental sciences

Other information

Authenticus ID: P-003-2TZ

DOI: 10.1186/1471-2148-10-281

Abstract (EN): Background: Cytosolic glutathione transferases (cGST) are a large group of ubiquitous enzymes involved in detoxification and are well known for their undesired side effects during chemotherapy. In this work we have performed thorough phylogenetic analyses to understand the various aspects of the evolution and functional diversification of cGSTs. Furthermore, we assessed plausible correlations between gene duplication and substrate specificity of gene paralogs in humans and selected species, notably in mammalian enzymes and their natural substrates. Results: We present a molecular phylogeny of cytosolic GSTs that shows that several classes of cGSTs are more ubiquitous and thus have an older ancestry than previously thought. Furthermore, we found that positive selection is implicated in the diversification of cGSTs. The number of duplicate genes per class is generally higher for groups of enzymes that metabolize products of oxidative damage. Conclusions: 1) Protection against oxidative stress seems to be the major driver of positive selection in mammalian cGSTs, explaining the overall expansion pattern of this subfamily; 2) Given the functional redundancy of GSTs that metabolize xenobiotic chemicals, we would expect the loss of gene duplicates, but by contrast we observed a gene expansion of this family, which likely has been favored by: i) the diversification of endogenous substrates; ii) differential tissue expression; and iii) increased specificity for a particular molecule; 3) The increased availability of sequence data from diversified taxa is likely to continue to improve our understanding of the early origin of the different cGST classes.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11