Skip to main content
Log in

In silico characterization and comparative genomic analysis of the Culex quinquefasciatus glutathione S-transferase (GST) supergene family

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

The glutathione S-transferases (GSTs) are phase II class of detoxification enzymes that are involved both directly and indirectly in insecticide resistance mechanisms. The Culex quinquefasciatus GST superfamily was analyzed by utilizing the public domain Culex genome sequence. In total, 35 cytosolic (seven classes) and 5 microsomal putatively active GSTs were retrieved, classified, and annotated. The study revealed the presence of three unclassified GSTs. Of 35 cytosolic GSTs, 65% contributed by insect specific Delta–Epsilon classes. Gene cluster analysis revealed that most of the genes of Delta, Epsilon, and Theta classes were organized into gene clusters. The gene organization analysis revealed the dominance of phase “0” introns in the Culex GST family. The studies on intron loss and gain events revealed that the Delta GSTs have experienced a higher number of loss and gains during their evolution. A positive correlation was observed between the phylogenetic relationship of members of the GST superfamily and their corresponding exon–intron organization. In addition, the genes within the gene clusters revealed the monophyletic phylogenetic relationship implying the importance of gene duplication events in the gene families' evolution. Finally, the comparative genomic analysis has shown a complex evolutionary scenario associated with the GST supergene family evolution in insects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Agianian B, Tucker PA, Schouten A, Leonard K, Bullard B, Gros P (2003) Structure of a Drosophila sigma class glutathione S-transferase reveals a novel active site topography suited for lipid peroxidation products. J Mol Biol 326:151–165

    Article  PubMed  CAS  Google Scholar 

  • Arensburger P, Megy K, Waterhouse R, Abrudan J, Amedeo P, Antelo B, Bartholomay L, Bidwell S, Caler E, Camara F, Campbell C, Campbell KS, Casola C, Castro M, Chandramouliswaran I, Chapman S, Christley S, Costas J, Eisenstadt E, Feschotte C, Fraser-Liggett CM, Guigo R, Haas B, Hammond M, Hansson B, Hemingway J, Hill S, Howarth C, Ignell R, Kennedy RC, Kodira C, Lobo NF, Mao C, Mayhew G, Michel K, Mori A, Liu N, Naveira HF, Nene V, Nguyen N, Pearson M, Pritham E, Puiu D, Qi Y, Ranson H, Ribeiro J, Roberston H, Severson DW, Shumway M, Stanke M, Strausberg RL, Sun C, Sutton G, Tu ZJ, Tubio JMC, Unger MF, Vanlandingham D, Vilella AJ, White O, White J, Wondji C, Wortman JR, Zdobnov E, Birren B, Christensen B, Collins FH, Cornel AJ, Dimopoulos G, Hannick L, Higgs S, Lanzaro G, Lawson D, Lee N, Muskavitch M, Raikhel A, Atkinson P (2010) Sequencing of Culex quinquefasciatus establishes a platform for mosquito comparative genomics. Science 330:86–88

    Article  PubMed  CAS  Google Scholar 

  • Betts MJ, Guigo R, Agarwal P, Russell RB (2001) Exon structure conservation despite low sequence similarity: a relic of dramatic events in evolution? EMBO J 20:5354–5360

    Article  PubMed  CAS  Google Scholar 

  • Blackburn AC, Woollatt E, Sutherland GR, Board PG (1998) Characterization and chromosome location of the gene GSTZ1 encoding the human Zeta class glutathione transferase and maleylacetoacetate isomerase. Cytogenet Cell Genet 83:109–114

    Article  PubMed  CAS  Google Scholar 

  • Board PG, Baker RT, Chelvanayagam G, Jermiin LS (1997) Zeta, a novel class of glutathione transferases in a range of species from plants to humans. Biochem J 328:929–935

    PubMed  CAS  Google Scholar 

  • Boudet N, Aubourg S, Toffano-Nioche C, Kreis M, Lecharny A (2001) Evolution of intron/exon structure of DEAD helicase family genes in Arabidopsis, Caenorhabditis, and Drosophila. Genome Res 11:2101–2114

    Article  PubMed  CAS  Google Scholar 

  • Castillo-Davis CI, Mekhedov SL, Hartl DL, Koonin EV, Kondrashov FA (2002) Selection for short introns in highly expressed genes. Nat Genet 31:415–418

    PubMed  CAS  Google Scholar 

  • Charif D, Thioulouse J, Lobry JR, Perrière G (2005) Online synonymous codon usage analyses with the ade4 and seqinR packages. Bioinformatics 21:545–547

    Article  PubMed  CAS  Google Scholar 

  • Chelvanayagam G, Parker MW, Board PG (2001) Fly fishing for GSTs: a unified nomenclature for mammalian and insect glutathione transferases. Chem Biol Interact 133:256–260

    CAS  Google Scholar 

  • Che-Mendoza A, Penilla RP, Rodriguez DA (2009) Insecticide resistance and glutathione S-transferases in mosquitoes: a review. Afr J Biotechnol 8:1386–1397

    CAS  Google Scholar 

  • Cho S, Jin SW, Cohen A, Ellis RE (2004) A phylogeny of Caenorhabditis reveals frequent loss of introns during nematode evolution. Genome Res 14:1207–1220

    Article  PubMed  CAS  Google Scholar 

  • Claudianos C, Ranson H, Johnson RM, Biswas S, Schuler MA, Berenbaum MR, Feyereisen R, Oakeshott JG (2006) A deficit of detoxification enzymes: pesticide sensitivity and environmental response in the honeybee. Insect Mol Biol 15:615–636

    Article  PubMed  CAS  Google Scholar 

  • Coulombe-Huntington J, Majewski J (2007) Intron loss and gain in Drosophila. Mol Biol Evol 24:2842–2850

    Article  PubMed  CAS  Google Scholar 

  • Csuros M (2005) Likely scenarios of intron evolution. Lect Notes Comput Sci 3678:47

    Article  Google Scholar 

  • DeBry RW, Slade NA (1985) Cladistic analysis of restriction endonuclease cleavage map data within a maximum likelihood framework. Syst Zool 31:21–34

    Article  Google Scholar 

  • Ding Y, Ortelli F, Rossiter LC, Hemingway J, Ranson H (2003) The Anopheles gambiae glutathione transferase supergene family: annotation, phylogeny and expression profiles. BMC Genomics 4:35

    Article  PubMed  Google Scholar 

  • Ding Y, Hawkes N, Meredith J, Eggleston P, Hemingway J, Ranson H (2005) Characterization of the promoters of Epsilon glutathione transferases in the mosquito Anopheles gambiae and their response to oxidative stress. Biochem J 387:879–888

    Article  PubMed  CAS  Google Scholar 

  • Dixon DP, Lapthorn A, Edwards R (2002) Plant glutathione transferases. Genome Biol 3(3):Reviews3004

    Google Scholar 

  • Dourado DF, Fernandes PA, Ramos MJ (2008) Mammalian cytosolic glutathione transferases. Curr Protein Pept Sci 9:325–337

    Article  PubMed  CAS  Google Scholar 

  • Enayati AA, Ranson H, Hemingway J (2005) Insect glutathione transferases and insecticide resistance. Insect Mol Biol 14:3–8

    Article  PubMed  CAS  Google Scholar 

  • Farris JS (1977) Phylogenetic analysis under Dollo's Law. Syst Zool 26:77–88

    Article  Google Scholar 

  • Feyereisen R (2006) Evolution of insect P450. Biochem Soc Trans 34:1252–1255

    Article  PubMed  CAS  Google Scholar 

  • Gotoh O (1998) Divergent structures of Caenorhabditis elegans cytochrome P450 genes suggest the frequent loss and gain of introns during the evolution of nematodes. Mol Biol Evol 15:1447–1459

    PubMed  CAS  Google Scholar 

  • Hayes JD, Pulford DJ (1995) The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30:521–600

    Article  Google Scholar 

  • Hemingway J, Field L, Vontas J (2002) An overview of insecticide resistance. Science 298:96–97

    Article  PubMed  CAS  Google Scholar 

  • Hemingway J, Beaty BJ, Rowland M, Scott TW, Sharp BL (2006) The Innovative Vector Control Consortium: improved control of mosquito-borne diseases. Trends Parasitol 22:308–312

    Article  PubMed  Google Scholar 

  • Henikoff S, Henikoff JG, Alford WJ, Pietrokovski S (1995) Automated construction and graphical presentation of protein blocks from unaligned sequences. Gene 163:GC17–GC26

    Article  PubMed  CAS  Google Scholar 

  • Huson DH, Steel M (2004) Phylogenetic trees based on gene content. Bioinformatics 20:2044–2049

    Article  PubMed  CAS  Google Scholar 

  • John HD, Jack FU, Ian JR (2005) Glutathione transferases. Annu Rev Pharmacol Toxicol 45:51–88

    Article  Google Scholar 

  • Kasai S, Komagata O, Okamura T, Tomita Y (2009) Alternative splicing and developmental regulation of glutathione transferases in Culex quinquefasciatus Say. Pestic Biochem Physiol 94:21–29

    Article  CAS  Google Scholar 

  • Knudsen AB, Slooff R (1992) Vector-borne disease problems in rapid urbanization: new approaches to vector control. Bull World Health Organ 70:1–6

    PubMed  CAS  Google Scholar 

  • Krauss V, Thummler C, Georgi F, Lehmann J, Stadler PF, Eisenhardt C (2008) Near intron positions are reliable phylogenetic markers: an application to holometabolous insects. Mol Biol Evol 25:821–830

    Article  PubMed  CAS  Google Scholar 

  • Le Quesne WJ (1974) The uniquely evolved character concept and its cladistic application. Syst Zool 23:513–517

    Article  Google Scholar 

  • Lin H, Zhu W, Silva J, Gu X, Buell CR (2006) Intron gain and loss in segmentally duplicated genes in rice. Genome Biol 7:R41

    Article  PubMed  Google Scholar 

  • Liska DJ (1998) The detoxification enzyme systems. Altern Med Rev 3:187–198

    PubMed  CAS  Google Scholar 

  • Long M, Thornton K (2001) Gene duplication and evolution. Science 293:1551

    Article  PubMed  CAS  Google Scholar 

  • Long M, Rosenberg C, Gilbert W (1995) Intron phase correlations and the evolution of the intron/exon structure of genes. Proc Natl Acad Sci USA 92:12495–12499

    Article  PubMed  CAS  Google Scholar 

  • Low WY, Ng HL, Morton CJ, Parker MW, Batterham P, Robin C (2007) Molecular evolution of glutathione S-transferases in the genus Drosophila. Genetics 177:1363

    Article  PubMed  CAS  Google Scholar 

  • Lumjuan N, Stevenson BJ, Prapanthadara L, Somboon P, Brophy PM, Loftus BJ, Severson DW, Ranson H (2007) The Aedes aegypti glutathione transferase family. Insect Biochem Mol Biol 37:1026–1035

    Article  PubMed  CAS  Google Scholar 

  • Mallet J (1989) The evolution of insecticide resistance: have the insects won? Trends Ecol Evol 4:336–340

    Article  PubMed  CAS  Google Scholar 

  • Mannervik B, Awasthi YC, Board PG, Hayes JD, Di Ilio C, Ketterer B, Listowsky I, Morgenstern R, Muramatsu M, Pearson WR (1992) Nomenclature for human glutathione transferases. Biochem J 282(Pt 1):305–306

    PubMed  CAS  Google Scholar 

  • Morel F, Rauch C, Coles B, Le Ferrec E, Guillouzo A (2002) The human glutathione transferase alpha locus: genomic organization of the gene cluster and functional characterization of the genetic polymorphism in the hGSTA1 promoter. Pharmacogenetics 12:277–286

    Article  PubMed  CAS  Google Scholar 

  • Muller P, Choua M, Pignatelli P, Etang J, Walker ED, Donnelly MJ, Simard F, Ranson H (2008) Pyrethroid tolerance is associated with elevated expression of antioxidants and agricultural practice in Anopheles arabiensis sampled from an area of cotton fields in Northern Cameroon. Mol Ecol 17:1145–1155

    Article  PubMed  CAS  Google Scholar 

  • Notredame C, Higgins DG, Heringa J (2000) T-Coffee: a novel method for fast and accurate multiple sequence alignment. J Mol Biol 302:205–217

    Article  PubMed  CAS  Google Scholar 

  • Oakeshott JG, Home I, Sutherland TD, Russell RJ (2003) The genomics of insecticide resistance. Genome Biol 4:202

    Article  PubMed  Google Scholar 

  • Paquette SM, Bak S, Feyereisen R (2000) Intron–exon organization and phylogeny in a large superfamily, the paralogous cytochrome P450 genes of Arabidopsis thaliana. DNA Cell Biol 19:307–317

    Article  PubMed  CAS  Google Scholar 

  • Pietrokovski S, Henikoff JG, Henikoff S (1996) The Blocks database—a system for protein classification. Nucleic Acids Res 24:197–200

    Article  PubMed  CAS  Google Scholar 

  • Ranson H, Hemingway J (2005) Glutathione transferases. Compr Mol Insect Sci 635:383–402

    Article  Google Scholar 

  • Ranson H, Claudianos C, Ortelli F, Abgrall C, Hemingway J, Sharakhova MV, Unger MF, Collins FH, Feyereisen R (2002) Evolution of supergene families associated with insecticide resistance. Science 298:179–181

    Article  PubMed  CAS  Google Scholar 

  • Rogozin IB, Wolf YI, Sorokin AV, Mirkin BG, Koonin EV (2003) Remarkable interkingdom conservation of intron positions and massive, lineage-specific intron loss and gain in eukaryotic evolution. Curr Biol 13:1512–1517

    Article  PubMed  CAS  Google Scholar 

  • Rogozin IB, Sverdlov AV, Babenko VN, Koonin EV (2005) Analysis of evolution of exon–intron structure of eukaryotic genes. Brief Bioinform 6:118–134

    Article  PubMed  CAS  Google Scholar 

  • Rokas A, Holland PWH (2000) Rare genomic changes as a tool for phylogenetics. Trends Ecol Evol 15:454–459

    Article  PubMed  Google Scholar 

  • Roy SW, Gilbert W (2005) Resolution of a deep animal divergence by the pattern of intron conservation. Proc Natl Acad Sci USA 102:4403–4408

    Article  PubMed  CAS  Google Scholar 

  • Roy SW, Penny D (2007) Intron length distributions and gene prediction. Nucleic Acids Res 35(14):4737–4742

    Article  PubMed  CAS  Google Scholar 

  • Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425

    PubMed  CAS  Google Scholar 

  • Sakarya O, Kosik KS, Oakley TH (2008) Reconstructing ancestral genome content based on symmetrical best alignments and Dollo parsimony. Bioinformatics 24:606–612

    Article  PubMed  CAS  Google Scholar 

  • Sanchez D, Ganfornina MD, Gutierrez G, Marin A (2003) Exon–intron structure and evolution of the Lipocalin gene family. Mol Biol Evol 20:775–783

    Article  PubMed  CAS  Google Scholar 

  • Saxena A, Hanukoglu I, Strautnieks SS, Thompson RJ, Gardiner RM, Hanukoglu A (1998) Gene structure of the human amiloride-sensitive epithelial sodium channel beta subunit. Biochem Biophys Res Commun 252:208–213

    Article  PubMed  CAS  Google Scholar 

  • Sheehan D, Meade G, Foley VM, Dowd CA (2001) Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily. Biochem J 360:1–16

    Article  PubMed  CAS  Google Scholar 

  • Soranzo N, Sari Gorla M, Mizzi L, De Toma G, Frova C (2004) Organisation and structural evolution of the rice glutathione S-transferase gene family. Mol Genet Genomics 271:511–521

    Article  PubMed  CAS  Google Scholar 

  • Stephen R, Gibbs RA, Weinstock GM, Beeman RW, Lorenzen MD, Lord JC, Oppert BS (2008) The genome of the model beetle and pest Tribolium castaneum. Nature 452:949–955

    Article  Google Scholar 

  • Tadepally H, Burger G, Aubry M (2008) Evolution of C2H2-zinc finger genes and subfamilies in mammals: species-specific duplication and loss of clusters, genes and effector domains. BMC Evol Biol 8:176

    Article  PubMed  Google Scholar 

  • Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599

    Article  PubMed  CAS  Google Scholar 

  • Thomas JH (2006) Concerted evolution of two novel protein families in Caenorhabditis species. Genetics 172(4):2269–2281

    Article  PubMed  CAS  Google Scholar 

  • Walters KB, Grant P, Johnson DLE (2009) Evolution of the GST omega gene family in 12 Drosophila species. J Hered 100:742–753

    Article  PubMed  CAS  Google Scholar 

  • Yang Z (2007) PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 24:1586–1591

    Article  PubMed  CAS  Google Scholar 

  • Zaim M, Guillet P (2002) Alternative insecticides: an urgent need. Trends Parasitol 18:161–163

    Article  PubMed  Google Scholar 

  • Zheng J, Rogozin IB, Koonin EV, Przytycka TM (2007) Support for the Coelomata clade of animals from a rigorous analysis of the pattern of intron conservation. Mol Biol Evol 24:2583–2592

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

BPNR was supported by Council of Scientific and Industrial Research (CSIR)-SRF fellowship. We gratefully acknowledge the continuous support provided by the Director-in-Charge, National Institute of Malaria Research, New Delhi.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to K. Raghavendra.

Electronic supplementary materials

Below is the link to the electronic supplementary material.

Online Resource 1

Diagrammatic representation of relative position of AgGSTU4 with respect to other Epsilon-class members of Anopheles gambiae (PDF 58 kb)

Online Resource 2

Plotcon-based multiple sequence graphical representation (PDF 26 kb)

Online Resource 3

Diagrammatic representation of Culex GST gene clusters identified in the genome (PDF 113 kb)

Online Resource 4

Phylogenetic analysis of Culex GSTs using maximum likelihood approach using PAML v4.0 (PDF 20 kb)

Online Resource 5

Inferring phylogenetic relationship among the members of C. quinquefasciatus GST supergene family based on Block sequences (PDF 137 kb)

Online Resource 6

Culex GST supergene family intron–exon length and gene organizations (PDF 216 kb)

Online Resource 7

GST class wise distribution of intron phases in Culex GST superfamily (PDF 71 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Niranjan Reddy, B.P., Prasad, G.B.K.S. & Raghavendra, K. In silico characterization and comparative genomic analysis of the Culex quinquefasciatus glutathione S-transferase (GST) supergene family. Parasitol Res 109, 1165–1177 (2011). https://doi.org/10.1007/s00436-011-2364-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-011-2364-x

Keywords

Navigation