GEPHE SUMMARY Print
Gephebase Gene
AHR
Entry Status
Published
GepheID
GP00001811
Main curator
Courtier
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
Gallus gallus - sensitive
Trait State in Taxon B
Sterna hirundo - tolerant
Ancestral State
Taxon A
Taxonomic Status
Taxon A
Latin Name
Common Name
chicken
Synonyms
Gallus gallus domesticus; chicken; bantam; chickens
Rank
species
Lineage
Show more ... pha; Tetrapoda; Amniota; Sauropsida; Sauria; Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda; Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae; Phasianinae; Gallus
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B
Common Name
-
Synonyms
Sterna hirundo hirundo Linnaeus, 1758
Rank
subspecies
Lineage
Show more ... etrapodomorpha; Tetrapoda; Amniota; Sauropsida; Sauria; Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda; Coelurosauria; Aves; Neognathae; Charadriiformes; Laridae; Sterna; Sterna hirundo
NCBI Taxonomy ID
is Taxon B an Infraspecies?
No
GENOTYPIC CHANGE
Generic Gene Name
Ahr
Synonyms
Ah; In; Ahh; Ahre; bHLHe76
Sequence Similarities
-
GO - Biological Process
GO:0045944 : positive regulation of transcription by RNA polymerase II ... show more
UniProtKB
Mus musculus
GenebankID or UniProtKB
Mutation #1
Presumptive Null
No
Molecular Type
Aberration Type
SNP
SNP Coding Change
Nonsynonymous
Molecular Details of the Mutation
V325I and A381S substitutions in the tern AHR converted the ligand-binding and transactivation abilities of the tern AHR to those of a chicken AHR- each substitution tested individually has an effect
Experimental Evidence
Taxon A Taxon B Position
Codon - - -
Amino-acid Val Ile 325
Authors
Karchner SI; Franks DG; Kennedy SW; Hahn ME
Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocarbons (HAHs) are highly toxic to most vertebrate animals, but there are dramatic differences in sensitivity among species and strains. Aquatic birds including the common tern (Sterna hirundo) are highly exposed to HAHs in the environment, but are up to 250-fold less sensitive to these compounds than the typical avian model, the domestic chicken (Gallus gallus). The mechanism of HAH toxicity involves altered gene expression subsequent to activation of the aryl hydrocarbon receptor (AHR), a basic helix-loop-helix-PAS transcription factor. AHR polymorphisms underlie mouse strain differences in sensitivity to HAHs and polynuclear aromatic hydrocarbons, but the role of the AHR in species differences in HAH sensitivity is not well understood. Here, we show that although chicken and tern AHRs both exhibit specific binding of [3H]TCDD, the tern AHR has a lower binding affinity and exhibits a reduced ability to support TCDD-dependent transactivation as compared to AHRs from chicken or mouse. We further show through use of chimeric AHR proteins and site-directed mutagenesis that the difference between the chicken and tern AHRs resides in the ligand-binding domain and that two amino acids (Val-325 and Ala-381) are responsible for the reduced activity of the tern AHR. Other avian species with reduced sensitivity to HAHs also possess these residues. These studies provide a molecular understanding of species differences in sensitivity to dioxin-like compounds and suggest an approach to using the AHR as a marker of dioxin susceptibility in wildlife.
Mutation #2
Presumptive Null
No
Molecular Type
Aberration Type
SNP
SNP Coding Change
Nonsynonymous
Molecular Details of the Mutation
V325I and A381S substitutions in the tern AHR converted the ligand-binding and transactivation abilities of the tern AHR to those of a chicken AHR- each substitution tested individually has an effect
Experimental Evidence
Taxon A Taxon B Position
Codon - - -
Amino-acid Ala Ser 381
Authors
Karchner SI; Franks DG; Kennedy SW; Hahn ME
Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocarbons (HAHs) are highly toxic to most vertebrate animals, but there are dramatic differences in sensitivity among species and strains. Aquatic birds including the common tern (Sterna hirundo) are highly exposed to HAHs in the environment, but are up to 250-fold less sensitive to these compounds than the typical avian model, the domestic chicken (Gallus gallus). The mechanism of HAH toxicity involves altered gene expression subsequent to activation of the aryl hydrocarbon receptor (AHR), a basic helix-loop-helix-PAS transcription factor. AHR polymorphisms underlie mouse strain differences in sensitivity to HAHs and polynuclear aromatic hydrocarbons, but the role of the AHR in species differences in HAH sensitivity is not well understood. Here, we show that although chicken and tern AHRs both exhibit specific binding of [3H]TCDD, the tern AHR has a lower binding affinity and exhibits a reduced ability to support TCDD-dependent transactivation as compared to AHRs from chicken or mouse. We further show through use of chimeric AHR proteins and site-directed mutagenesis that the difference between the chicken and tern AHRs resides in the ligand-binding domain and that two amino acids (Val-325 and Ala-381) are responsible for the reduced activity of the tern AHR. Other avian species with reduced sensitivity to HAHs also possess these residues. These studies provide a molecular understanding of species differences in sensitivity to dioxin-like compounds and suggest an approach to using the AHR as a marker of dioxin susceptibility in wildlife.
RELATED GEPHE
Related Genes
Related Haplotypes
No matches found.
EXTERNAL LINKS
COMMENTS
Mutation in AHR2 is protective of toxicity in killifish, tomcod and mice Ala-381 in the tern AHR is homologous to (i.e. at the equivalent position as) Ala-375 of the high-affinity mouse Ahb−1 protein and Val-375 and Val-380 of the lower-affinity mouse Ahd and human AHR proteins; respectively - Val > Ala > Ser at this position appear to form a series of substitutions leading to increasing stability of TCDD interaction with the AHR @& taxonID did not fetch species name
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