Comparative genomics identifies new alpha class genes within the avian glutathione S-transferase gene cluster

Ji Eun Kim; Miranda M. Bauer; Kristelle M. Mendoza; Kent M. Reed; Roger A. Coulombe

doi:10.1016/j.gene.2009.11.001

Comparative genomics identifies new alpha class genes within the avian glutathione S-transferase gene cluster

Ji Eun Kim, Miranda M. Bauer, Kristelle M. Mendoza, Kent M. Reed, Roger A. Coulombe

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Glutathione S-transferases (GSTs: EC2.5.1.18) are a superfamily of multifunctional dimeric enzymes that catalyze the conjugation of glutathione (GSH) to electrophilic chemicals. In most animals and in humans, GSTs are the principal enzymes responsible for detoxifying the mycotoxin aflatoxin B₁ (AFB₁) and GST dysfunction is a known risk factor for susceptibility towards AFB₁. Turkeys are one of the most susceptible animals known to AFB₁, which is a common contaminant of poultry feeds. The extreme susceptibility of turkeys is associated with hepatic GSTs unable to detoxify the highly reactive and electrophilic metabolite exo-AFB₁-8,9-epoxide (AFBO). In this study, comparative genomic approaches were used to amplify and identify the α-class tGST genes (tGSTA1.1, tGSTA1.2, tGSTA1.3, tGSTA2, tGSTA3 and tGSTA4) from turkey liver. The conserved GST domains and four α-class signature motifs in turkey GSTs (with the exception of tGSTA1.1 which lacked one motif) confirm the presence of hepatic α-class GSTs in the turkey. Four signature motifs and conserved residues found in α-class tGSTs are (1) xMExxxWLLAAAGVE, (2) YGKDxKERAxIDMYVxG, (3) PVxEKVLKxHGxxxL and (4) PxIKKFLXPGSxxKPxxx. A BAC clone containing the α-class GST gene cluster was isolated and sequenced. The turkey α-class GTS genes genetically map to chromosome MGA2 with synteny between turkey and human α-class GSTs and flanking genes. This study identifies the α-class tGST gene cluster and genetic markers (SNPs, single nucleotide polymorphisms) that can be used to further examine AFB₁ susceptibility and resistance in turkeys. Functional characterization of heterologously expressed proteins from these genes is currently underway.

Original language	English (US)
Pages (from-to)	45-53
Number of pages	9
Journal	Gene
Volume	452
Issue number	2
DOIs	https://doi.org/10.1016/j.gene.2009.11.001
State	Published - Mar 2010

Bibliographical note

Funding Information:
The authors thank L.D. Chaves for assistance in BAC screening and sequence annotation. We also thank Dr. Lynn Bagley of the Moroni Feed Cooperative for generously providing turkeys and feed for this study. This research was supported in part by NRI competitive grant 2004-35205-14217 from the USDA-CSREES , by competitive grant 2007-35205-17880 from the USDA CSREES , Animal Genome program, and support from the Minnesota, and Utah and Agricultural Experiment Stations, where this is published as paper 8122.

Keywords

Aflatoxin B1
BAC
Detoxification
Glutathione S-transferases
Mapping
SNP

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10.1016/j.gene.2009.11.001

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title = "Comparative genomics identifies new alpha class genes within the avian glutathione S-transferase gene cluster",

abstract = "Glutathione S-transferases (GSTs: EC2.5.1.18) are a superfamily of multifunctional dimeric enzymes that catalyze the conjugation of glutathione (GSH) to electrophilic chemicals. In most animals and in humans, GSTs are the principal enzymes responsible for detoxifying the mycotoxin aflatoxin B1 (AFB1) and GST dysfunction is a known risk factor for susceptibility towards AFB1. Turkeys are one of the most susceptible animals known to AFB1, which is a common contaminant of poultry feeds. The extreme susceptibility of turkeys is associated with hepatic GSTs unable to detoxify the highly reactive and electrophilic metabolite exo-AFB1-8,9-epoxide (AFBO). In this study, comparative genomic approaches were used to amplify and identify the α-class tGST genes (tGSTA1.1, tGSTA1.2, tGSTA1.3, tGSTA2, tGSTA3 and tGSTA4) from turkey liver. The conserved GST domains and four α-class signature motifs in turkey GSTs (with the exception of tGSTA1.1 which lacked one motif) confirm the presence of hepatic α-class GSTs in the turkey. Four signature motifs and conserved residues found in α-class tGSTs are (1) xMExxxWLLAAAGVE, (2) YGKDxKERAxIDMYVxG, (3) PVxEKVLKxHGxxxL and (4) PxIKKFLXPGSxxKPxxx. A BAC clone containing the α-class GST gene cluster was isolated and sequenced. The turkey α-class GTS genes genetically map to chromosome MGA2 with synteny between turkey and human α-class GSTs and flanking genes. This study identifies the α-class tGST gene cluster and genetic markers (SNPs, single nucleotide polymorphisms) that can be used to further examine AFB1 susceptibility and resistance in turkeys. Functional characterization of heterologously expressed proteins from these genes is currently underway.",

keywords = "Aflatoxin B1, BAC, Detoxification, Glutathione S-transferases, Mapping, SNP",

author = "Kim, {Ji Eun} and Bauer, {Miranda M.} and Mendoza, {Kristelle M.} and Reed, {Kent M.} and Coulombe, {Roger A.}",

note = "Funding Information: The authors thank L.D. Chaves for assistance in BAC screening and sequence annotation. We also thank Dr. Lynn Bagley of the Moroni Feed Cooperative for generously providing turkeys and feed for this study. This research was supported in part by NRI competitive grant 2004-35205-14217 from the USDA-CSREES , by competitive grant 2007-35205-17880 from the USDA CSREES , Animal Genome program, and support from the Minnesota, and Utah and Agricultural Experiment Stations, where this is published as paper 8122.",

year = "2010",

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doi = "10.1016/j.gene.2009.11.001",

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AU - Kim, Ji Eun

AU - Bauer, Miranda M.

AU - Mendoza, Kristelle M.

AU - Reed, Kent M.

AU - Coulombe, Roger A.

N1 - Funding Information: The authors thank L.D. Chaves for assistance in BAC screening and sequence annotation. We also thank Dr. Lynn Bagley of the Moroni Feed Cooperative for generously providing turkeys and feed for this study. This research was supported in part by NRI competitive grant 2004-35205-14217 from the USDA-CSREES , by competitive grant 2007-35205-17880 from the USDA CSREES , Animal Genome program, and support from the Minnesota, and Utah and Agricultural Experiment Stations, where this is published as paper 8122.

PY - 2010/3

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N2 - Glutathione S-transferases (GSTs: EC2.5.1.18) are a superfamily of multifunctional dimeric enzymes that catalyze the conjugation of glutathione (GSH) to electrophilic chemicals. In most animals and in humans, GSTs are the principal enzymes responsible for detoxifying the mycotoxin aflatoxin B1 (AFB1) and GST dysfunction is a known risk factor for susceptibility towards AFB1. Turkeys are one of the most susceptible animals known to AFB1, which is a common contaminant of poultry feeds. The extreme susceptibility of turkeys is associated with hepatic GSTs unable to detoxify the highly reactive and electrophilic metabolite exo-AFB1-8,9-epoxide (AFBO). In this study, comparative genomic approaches were used to amplify and identify the α-class tGST genes (tGSTA1.1, tGSTA1.2, tGSTA1.3, tGSTA2, tGSTA3 and tGSTA4) from turkey liver. The conserved GST domains and four α-class signature motifs in turkey GSTs (with the exception of tGSTA1.1 which lacked one motif) confirm the presence of hepatic α-class GSTs in the turkey. Four signature motifs and conserved residues found in α-class tGSTs are (1) xMExxxWLLAAAGVE, (2) YGKDxKERAxIDMYVxG, (3) PVxEKVLKxHGxxxL and (4) PxIKKFLXPGSxxKPxxx. A BAC clone containing the α-class GST gene cluster was isolated and sequenced. The turkey α-class GTS genes genetically map to chromosome MGA2 with synteny between turkey and human α-class GSTs and flanking genes. This study identifies the α-class tGST gene cluster and genetic markers (SNPs, single nucleotide polymorphisms) that can be used to further examine AFB1 susceptibility and resistance in turkeys. Functional characterization of heterologously expressed proteins from these genes is currently underway.

AB - Glutathione S-transferases (GSTs: EC2.5.1.18) are a superfamily of multifunctional dimeric enzymes that catalyze the conjugation of glutathione (GSH) to electrophilic chemicals. In most animals and in humans, GSTs are the principal enzymes responsible for detoxifying the mycotoxin aflatoxin B1 (AFB1) and GST dysfunction is a known risk factor for susceptibility towards AFB1. Turkeys are one of the most susceptible animals known to AFB1, which is a common contaminant of poultry feeds. The extreme susceptibility of turkeys is associated with hepatic GSTs unable to detoxify the highly reactive and electrophilic metabolite exo-AFB1-8,9-epoxide (AFBO). In this study, comparative genomic approaches were used to amplify and identify the α-class tGST genes (tGSTA1.1, tGSTA1.2, tGSTA1.3, tGSTA2, tGSTA3 and tGSTA4) from turkey liver. The conserved GST domains and four α-class signature motifs in turkey GSTs (with the exception of tGSTA1.1 which lacked one motif) confirm the presence of hepatic α-class GSTs in the turkey. Four signature motifs and conserved residues found in α-class tGSTs are (1) xMExxxWLLAAAGVE, (2) YGKDxKERAxIDMYVxG, (3) PVxEKVLKxHGxxxL and (4) PxIKKFLXPGSxxKPxxx. A BAC clone containing the α-class GST gene cluster was isolated and sequenced. The turkey α-class GTS genes genetically map to chromosome MGA2 with synteny between turkey and human α-class GSTs and flanking genes. This study identifies the α-class tGST gene cluster and genetic markers (SNPs, single nucleotide polymorphisms) that can be used to further examine AFB1 susceptibility and resistance in turkeys. Functional characterization of heterologously expressed proteins from these genes is currently underway.

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Comparative genomics identifies new alpha class genes within the avian glutathione S-transferase gene cluster

Abstract

Bibliographical note

Keywords

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