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The strong selective sweep candidate gene ADRA2C does not explain domestication related changes in the stress response of chickens.

Elfwing M, Fallahshahroudi A, Lindgren I, Jensen P, Altimiras J - PLoS ONE (2014)

Bottom Line: In hypothalamus and amygdala, regions associated with the stress response, and in striatum, receptor binding pIC50 values ranged between 8.1-8.4, and the level was not influenced by the genotyped allele.We did not find compelling genotype effects in open field, tonic immobility, aerial predator, associative learning or fecundity.Therefore we conclude that ADRA2C is probably not involved in the domestication of the stress response in chicken, and the strong selective sweep is probably caused by selection of some unknown genetic element in the vicinity of the gene.

View Article: PubMed Central - PubMed

Affiliation: AVIAN Behavioural Genomics and Physiology Group, Division of Biology, IFM Biology, Linköping University, Linköping, Sweden.

ABSTRACT
Analysis of selective sweeps to pinpoint causative genomic regions involved in chicken domestication has revealed a strong selective sweep on chromosome 4 in layer chickens. The autoregulatory α-adrenergic receptor 2C (ADRA2C) gene is the closest to the selective sweep and was proposed as an important gene in the domestication of layer chickens. The ADRA2C promoter region was also hypermethylated in comparison to the non-selected ancestor of all domesticated chicken breeds, the Red Junglefowl, further supporting its relevance. In mice the receptor is involved in the fight-or-flight response as it modulates epinephrine release from the adrenals. To investigate the involvement of ADRA2C in chicken domestication, we measured gene expression in the adrenals and radiolabeled receptor ligand in three brain regions comparing the domestic White Leghorn strain with the wild ancestor Red Junglefowl. In adrenals ADRA2C was twofold greater expressed than the related receptor gene ADRA2A, indicating that ADRA2C is the predominant modulator of epinephrine release but no strain differences were measured. In hypothalamus and amygdala, regions associated with the stress response, and in striatum, receptor binding pIC50 values ranged between 8.1-8.4, and the level was not influenced by the genotyped allele. Because chicken strains differ in morphology, physiology and behavior, differences attributed to a single gene may be lost in the noise caused by the heterogeneous genetic background. Therefore an F10 advanced intercross strain between White Leghorn and Red Junglefowl was used to investigate effects of ADRA2C alleles on fear related behaviors and fecundity. We did not find compelling genotype effects in open field, tonic immobility, aerial predator, associative learning or fecundity. Therefore we conclude that ADRA2C is probably not involved in the domestication of the stress response in chicken, and the strong selective sweep is probably caused by selection of some unknown genetic element in the vicinity of the gene.

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Positional information on the location of ADRA2C in relation to a neighboring selective sweep and methylated regions from previous studies.A) Location of the ADRA2C in chromosome 4 in relation to the selective sweep region reported by Rubin et al. (2010). All coordinates are expressed as kb. The position of the 1229 bp long gene starting at 84590769 is represented by a blue box and the SNP in position 84590997 used for genotyping is shown as a yellow star within the gene. The direction of transcription is indicated with an arrow. The methylation pattern bp long gene starting at 84590769 is represented by a blue box and the SNP in position 84590997 used for genotyping is shown as a yellow star within the gene. The direction of transcription is indicated with an arrow. The methylation pattern (in Log2 fold change) comparing RJF and WL, shown with a resolution of 50–75 bp regions is shown in the bar graph, and the hypermethylated region is highlighted with a red bar at position 84593087. Methylation data from N bp regions is shown in the bar graph, and the hypermethylated region is highlighted with a red bar at position 84593087. Methylation data from Nätt et al. [16]. B) Peptide sequence homology phylogeny of the annotated sequences of α2 adrenergic receptor subtypes cluster the chicken ADRA2C gene to better characterized mammalian ADRA2C genes.
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pone-0103218-g001: Positional information on the location of ADRA2C in relation to a neighboring selective sweep and methylated regions from previous studies.A) Location of the ADRA2C in chromosome 4 in relation to the selective sweep region reported by Rubin et al. (2010). All coordinates are expressed as kb. The position of the 1229 bp long gene starting at 84590769 is represented by a blue box and the SNP in position 84590997 used for genotyping is shown as a yellow star within the gene. The direction of transcription is indicated with an arrow. The methylation pattern bp long gene starting at 84590769 is represented by a blue box and the SNP in position 84590997 used for genotyping is shown as a yellow star within the gene. The direction of transcription is indicated with an arrow. The methylation pattern (in Log2 fold change) comparing RJF and WL, shown with a resolution of 50–75 bp regions is shown in the bar graph, and the hypermethylated region is highlighted with a red bar at position 84593087. Methylation data from N bp regions is shown in the bar graph, and the hypermethylated region is highlighted with a red bar at position 84593087. Methylation data from Nätt et al. [16]. B) Peptide sequence homology phylogeny of the annotated sequences of α2 adrenergic receptor subtypes cluster the chicken ADRA2C gene to better characterized mammalian ADRA2C genes.

Mentions: The position of the 120 kb long selective sweep window stretches between chr4:84.46–84.58 mb [12] in ENSEMBL WASHUC2 database. ADRA2C consists of a single 1229 bp long exon starting at chr4:84590769 transcribed 3′ to 5′ and situated 10 769 bp from the selective sweep. The significant hypermethylation in the presumed promoter region consists of a differentially methylated 50 bp-region located at chr4:84593087, a pattern seen regularly as an epigenetic modification [16] (Figure 1A).


The strong selective sweep candidate gene ADRA2C does not explain domestication related changes in the stress response of chickens.

Elfwing M, Fallahshahroudi A, Lindgren I, Jensen P, Altimiras J - PLoS ONE (2014)

Positional information on the location of ADRA2C in relation to a neighboring selective sweep and methylated regions from previous studies.A) Location of the ADRA2C in chromosome 4 in relation to the selective sweep region reported by Rubin et al. (2010). All coordinates are expressed as kb. The position of the 1229 bp long gene starting at 84590769 is represented by a blue box and the SNP in position 84590997 used for genotyping is shown as a yellow star within the gene. The direction of transcription is indicated with an arrow. The methylation pattern bp long gene starting at 84590769 is represented by a blue box and the SNP in position 84590997 used for genotyping is shown as a yellow star within the gene. The direction of transcription is indicated with an arrow. The methylation pattern (in Log2 fold change) comparing RJF and WL, shown with a resolution of 50–75 bp regions is shown in the bar graph, and the hypermethylated region is highlighted with a red bar at position 84593087. Methylation data from N bp regions is shown in the bar graph, and the hypermethylated region is highlighted with a red bar at position 84593087. Methylation data from Nätt et al. [16]. B) Peptide sequence homology phylogeny of the annotated sequences of α2 adrenergic receptor subtypes cluster the chicken ADRA2C gene to better characterized mammalian ADRA2C genes.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4128585&req=5

pone-0103218-g001: Positional information on the location of ADRA2C in relation to a neighboring selective sweep and methylated regions from previous studies.A) Location of the ADRA2C in chromosome 4 in relation to the selective sweep region reported by Rubin et al. (2010). All coordinates are expressed as kb. The position of the 1229 bp long gene starting at 84590769 is represented by a blue box and the SNP in position 84590997 used for genotyping is shown as a yellow star within the gene. The direction of transcription is indicated with an arrow. The methylation pattern bp long gene starting at 84590769 is represented by a blue box and the SNP in position 84590997 used for genotyping is shown as a yellow star within the gene. The direction of transcription is indicated with an arrow. The methylation pattern (in Log2 fold change) comparing RJF and WL, shown with a resolution of 50–75 bp regions is shown in the bar graph, and the hypermethylated region is highlighted with a red bar at position 84593087. Methylation data from N bp regions is shown in the bar graph, and the hypermethylated region is highlighted with a red bar at position 84593087. Methylation data from Nätt et al. [16]. B) Peptide sequence homology phylogeny of the annotated sequences of α2 adrenergic receptor subtypes cluster the chicken ADRA2C gene to better characterized mammalian ADRA2C genes.
Mentions: The position of the 120 kb long selective sweep window stretches between chr4:84.46–84.58 mb [12] in ENSEMBL WASHUC2 database. ADRA2C consists of a single 1229 bp long exon starting at chr4:84590769 transcribed 3′ to 5′ and situated 10 769 bp from the selective sweep. The significant hypermethylation in the presumed promoter region consists of a differentially methylated 50 bp-region located at chr4:84593087, a pattern seen regularly as an epigenetic modification [16] (Figure 1A).

Bottom Line: In hypothalamus and amygdala, regions associated with the stress response, and in striatum, receptor binding pIC50 values ranged between 8.1-8.4, and the level was not influenced by the genotyped allele.We did not find compelling genotype effects in open field, tonic immobility, aerial predator, associative learning or fecundity.Therefore we conclude that ADRA2C is probably not involved in the domestication of the stress response in chicken, and the strong selective sweep is probably caused by selection of some unknown genetic element in the vicinity of the gene.

View Article: PubMed Central - PubMed

Affiliation: AVIAN Behavioural Genomics and Physiology Group, Division of Biology, IFM Biology, Linköping University, Linköping, Sweden.

ABSTRACT
Analysis of selective sweeps to pinpoint causative genomic regions involved in chicken domestication has revealed a strong selective sweep on chromosome 4 in layer chickens. The autoregulatory α-adrenergic receptor 2C (ADRA2C) gene is the closest to the selective sweep and was proposed as an important gene in the domestication of layer chickens. The ADRA2C promoter region was also hypermethylated in comparison to the non-selected ancestor of all domesticated chicken breeds, the Red Junglefowl, further supporting its relevance. In mice the receptor is involved in the fight-or-flight response as it modulates epinephrine release from the adrenals. To investigate the involvement of ADRA2C in chicken domestication, we measured gene expression in the adrenals and radiolabeled receptor ligand in three brain regions comparing the domestic White Leghorn strain with the wild ancestor Red Junglefowl. In adrenals ADRA2C was twofold greater expressed than the related receptor gene ADRA2A, indicating that ADRA2C is the predominant modulator of epinephrine release but no strain differences were measured. In hypothalamus and amygdala, regions associated with the stress response, and in striatum, receptor binding pIC50 values ranged between 8.1-8.4, and the level was not influenced by the genotyped allele. Because chicken strains differ in morphology, physiology and behavior, differences attributed to a single gene may be lost in the noise caused by the heterogeneous genetic background. Therefore an F10 advanced intercross strain between White Leghorn and Red Junglefowl was used to investigate effects of ADRA2C alleles on fear related behaviors and fecundity. We did not find compelling genotype effects in open field, tonic immobility, aerial predator, associative learning or fecundity. Therefore we conclude that ADRA2C is probably not involved in the domestication of the stress response in chicken, and the strong selective sweep is probably caused by selection of some unknown genetic element in the vicinity of the gene.

Show MeSH
Related in: MedlinePlus