Biology Faculty Articles

Document Type

Article

Publication Date

2010

Publication Title

BMC Evolutionary Biology

ISSN

1471-2148

Volume

10

Issue/No.

281

First Page

1

Last Page

11

Abstract

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.

Comments

©da Fonseca et al. 2010

Additional Comments

FCT grant #: SFRH/BPD/26769/2006; Portuguese Foundation for Science and Technology project #s: PTDC/BIA-BDE/69144/2006, PTDC/AAC-AMB/104983/2008

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

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