| 1. |
- Cardoso-Moreira, Margarida, et al.
(författare)
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Gene expression across mammalian organ development
- 2019
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 571:7766, s. 505-
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of gene expression in mammalian organ development remains largely uncharacterized. Here we report the transcriptomes of seven organs (cerebrum, cerebellum, heart, kidney, liver, ovary and testis) across developmental time points from early organogenesis to adulthood for human, rhesus macaque, mouse, rat, rabbit, opossum and chicken. Comparisons of gene expression patterns identified correspondences of developmental stages across species, and differences in the timing of key events during the development of the gonads. We found that the breadth of gene expression and the extent of purifying selection gradually decrease during development, whereas the amount of positive selection and expression of new genes increase. We identified differences in the temporal trajectories of expression of individual genes across species, with brain tissues showing the smallest percentage of trajectory changes, and the liver and testis showing the largest. Our work provides a resource of developmental transcriptomes of seven organs across seven species, and comparative analyses that characterize the development and evolution of mammalian organs.
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| 2. |
- Elfwing, Magnus, et al.
(författare)
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The Strong Selective Sweep Candidate Gene ADRA2C Does Not Explain Domestication Related Changes In The Stress Response Of Chickens
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 9:8, s. e103218-
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of selective sweeps to pinpoint causative genomic regions involved in chicken domestication has revealed a strongselective sweep on chromosome 4 in layer chickens. The autoregulatory a-adrenergic receptor 2C (ADRA2C) gene is theclosest to the selective sweep and was proposed as an important gene in the domestication of layer chickens. The ADRA2Cpromoter 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 itmodulates epinephrine release from the adrenals. To investigate the involvement of ADRA2C in chicken domestication, wemeasured gene expression in the adrenals and radiolabeled receptor ligand in three brain regions comparing the domesticWhite Leghorn strain with the wild ancestor Red Junglefowl. In adrenals ADRA2C was twofold greater expressed than therelated receptor gene ADRA2A, indicating that ADRA2C is the predominant modulator of epinephrine release but no straindifferences 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. Becausechicken strains differ in morphology, physiology and behavior, differences attributed to a single gene may be lost in thenoise caused by the heterogeneous genetic background. Therefore an F10 advanced intercross strain between WhiteLeghorn and Red Junglefowl was used to investigate effects of ADRA2C alleles on fear related behaviors and fecundity. Wedid 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 thestrong selective sweep is probably caused by selection of some unknown genetic element in the vicinity of the gene.
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| 3. |
- Fallahshahroudi, Amir, et al.
(författare)
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Domestication Effects on Stress Induced Steroid Secretion and Adrenal Gene Expression in Chickens
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the genetic basis of phenotypic diversity is a challenge in contemporary biology. Domestication provides a model for unravelling aspects of the genetic basis of stress sensitivity. The ancestral Red Junglefowl (RJF) exhibits greater fear-related behaviour and a more pronounced HPA-axis reactivity than its domesticated counterpart, the White Leghorn (WL). By comparing hormones (plasmatic) and adrenal global gene transcription profiles between WL and RJF in response to an acute stress event, we investigated the molecular basis for the altered physiological stress responsiveness in domesticated chickens. Basal levels of pregnenolone and dehydroepiandrosterone as well as corticosterone response were lower in WL. Microarray analysis of gene expression in adrenal glands showed a significant breed effect in a large number of transcripts with over-representation of genes in the channel activity pathway. The expression of the best-known steroidogenesis genes were similar across the breeds used. Transcription levels of acute stress response genes such as StAR, CH25 and POMC were upregulated in response to acute stress. Dampened HPA reactivity in domesticated chickens was associated with changes in the expression of several genes that presents potentially minor regulatory effects rather than by means of change in expression of critical steroidogenic genes in the adrenal.
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| 4. |
- Fallahshahroudi, Amir, 1981-
(författare)
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Domestication Effects on the Stress Response in Chickens : Genetics, Physiology, and Behaviour
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Animal domestication, the process where animals become adapted to living in proximity to humans, is associated with the alteration of multiple traits, including decreased fearfulness and stress response. With an estimated population of 50 billion, the domesticated chicken is the most populous avian species in the world. Hundreds of chicken breeds have been developed for meat and egg production, hobby or research purposes. Multidirectional selection and the relaxation of natural selection in captivity have created immense phenotypic diversity amongst domesticates in a relatively short evolutionary time. The extensive phenotypic diversity, existence of the wild ancestor, and feasibility of intercrossing various breeds makes the chicken a suitable model animal for deciphering genetic determinants of complex traits such as stress response. We used chicken domestication as a model to gain insights about the mechanisms that regulate stress response in an avian species. We studied behavioural and physiological stress response in the ancestral Red Junglefowl and one of its domesticated progenies, White Leghorn. An advanced intercross between the aforementioned breeds was later used to map genetic loci underlying modification of stress response. The general pattern of the stress response in chickens was comparable with that reported in mammals, however we identified distinctive differences in the stress modulatory pathways in chickens. We showed that changes in the expression levels of several stress modulatory genes in the brain, the pituitary and the adrenal glands underlie the observed modified stress response in domesticated chickens. Using quantitative trait loci (QTL) mapping, several QTL underlying stress induced corticosterone, aldosterone and baseline dehydroepiandrosterone (DHEA) levels were detected. As a next step, we combined QTL mapping with gene expression (eQTL) mapping and narrowed two QTL down to the putative causal genes, SERPINA10 and PDE1C. Both of these genes were differentially expressed in the adrenal glands of White Leghorn and the Red Junglefowl, had overlapping eQTL with hormonal QTL, and their expression levels in the adrenal glands were correlated with plasma levels of corticosterone and al-dosterone. These two genes thus serve as strong candidates for further functional investigation concerning modification of the stress response during domestication. This dissertation increase the knowledge about genetics and physiology of the stress response in an avian species and its modification during domestication. Our findings expand the basic knowledge about the stress response in chicken, which can potentially be used to improve welfare through appropriate genetic selection.
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| 5. |
- Fallahshahroudi, Amir, et al.
(författare)
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Effects of the domestic thyroid stimulating hormone receptor (TSHR) variant on the hypothalamic-pituitary-thyroid axis and behavior in chicken
- 2021
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Ingår i: Genetics. - : Oxford University Press. - 0016-6731 .- 1943-2631. ; 217:1
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Tidskriftsartikel (refereegranskat)abstract
- Domestic chickens are less fearful, have a faster sexual development, grow bigger, and lay more eggs than their primary ancestor, the red junglefowl. Several candidate genetic variants selected during domestication have been identified, but only a few studies have directly linked them with distinct phenotypic traits. Notably, a variant of the thyroid stimulating hormone receptor (TSHR) gene has been under strong positive selection over the past millennium, but it’s function and mechanisms of action are still largely unresolved. We therefore assessed the abundance of the domestic TSHR variant and possible genomic selection signatures in an extensive data set comprising multiple commercial and village chicken populations as well as wild-living extant members of the genus Gallus. Furthermore, by mean of extensive backcrossing we introgressed the wild-type TSHR variant from red junglefowl into domestic White Leghorn chickens and investigated gene expression, hormone levels, cold adaptation, and behavior in chickens possessing either the wild-type or domestic TSHR variant. While the domestic TSHR was the most common variant in all studied domestic populations and in one of two red junglefowl population, it was not detected in the other Gallus species. Functionally, the individuals with the domestic TSHR variant had a lower expression of the TSHR in the hypothalamus and marginally higher in the thyroid gland than wild-type TSHR individuals. Expression of TSHB and DIO2, two regulators of sexual maturity and reproduction in birds, was higher in the pituitary gland of the domestic-variant chickens. Furthermore, the domestic variant was associated with higher activity in the open field test. Our findings confirm that the spread of the domestic TSHR variant is limited to domesticated chickens, and to a lesser extent, their wild counterpart, the red junglefowl. Furthermore, we showed that effects of genetic variability in TSHR mirror key differences in gene expression and behavior previously described between the red junglefowl and domestic chicken.
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| 6. |
- Fallahshahroudi, Amir, et al.
(författare)
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Genetic and Targeted eQTL Mapping Reveals Strong Candidate Genes Modulating the Stress Response During Chicken Domestication.
- 2017
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Ingår i: G3. - : The Genetics Society. - 2160-1836. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- The stress response has been largely modified in all domesticated animals, offering a strong tool for genetic mapping. In chickens, ancestral Red Junglefowl react stronger both in terms of physiology and behavior to a brief restraint stress than domesticated White Leghorn, demonstrating modified functions of the hypothalamic-pituitary-adrenal (HPA) axis. We mapped quantitative trait loci (QTL) underlying variations in stress-induced hormone levels using 232 birds from the 12th generation of an advanced intercross between White Leghorn and Red Junglefowl, genotyped for 739 genetic markers. Plasma levels of corticosterone, dehydroepiandrosterone (DHEA), and pregnenolone (PREG) were measured using LC-MS/MS in all genotyped birds. Transcription levels of the candidate genes were measured in the adrenal glands or hypothalamus of 88 out of the 232 birds used for hormone assessment. Genes were targeted for expression analysis when they were located in a hormone QTL region and were differentially expressed in the pure breed birds. One genome-wide significant QTL on chromosome 5 and two suggestive QTL together explained 20% of the variance in corticosterone response. Two significant QTL for aldosterone on chromosome 2 and 5 (explaining 19% of the variance), and one QTL for DHEA on chromosome 4 (explaining 5% of the variance), were detected. Orthologous DNA regions to the significant corticosterone QTL have been previously associated with the physiological stress response in other species but, to our knowledge, the underlying gene(s) have not been identified. SERPINA10 had an expression QTL (eQTL) colocalized with the corticosterone QTL on chromosome 5 and PDE1C had an eQTL colocalized with the aldosterone QTL on chromosome 2. Furthermore, in both cases, the expression levels of the genes were correlated with the plasma levels of the hormones. Hence, both these genes are strong putative candidates for the domestication-induced modifications of the stress response in chickens. Improved understanding of the genes associated with HPA-axis reactivity can provide insights into the pathways and mechanisms causing stress-related pathologies.
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| 7. |
- Fallahshahroudi, Amir, et al.
(författare)
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The Domestic BCO2 Allele Buffers Low-Carotenoid Diets in Chickens : Possible Fitness Increase Through Species Hybridization
- 2019
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Ingår i: Genetics. - : GENETICS SOCIETY AMERICA. - 0016-6731 .- 1943-2631. ; 212:4, s. 1445-1452
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Tidskriftsartikel (refereegranskat)abstract
- Domestic animals are adapted to conditions vastly different from those of their wild ancestors, and this is particularly true for their diets. The most numerous of all domestic species, the chicken, originated from the Red Junglefowl (RJF), a native of subtropical forests in Southeast Asia. Surprisingly however, in domestic chicken breeds, a common haplotype of the beta-carotene oxygenase 2 (BCO2) gene, which is involved in carotenoid metabolism, is introgressed from a related species, the Gray Junglefowl, and has been under strong selective pressure during domestication. This suggests that a hybridization event may have conferred a fitness advantage on chickens carrying the derived allele. To investigate the possible biological function of the introgressed BCO2 allele in chicken, we introgressed the ancestral BCO2 allele into domestic White Leghorn chickens. We measured gene expression as well as carotenoid accumulation in skin and eggs of chickens carrying either the ancestral or the derived BCO2 allele. The derived haplotype was associated with down-regulation of BCO2 in skin, muscle, and adipose tissue, but not in liver or duodenum, indicating that carotenoid accumulation occurred in the tissues with reduced gene expression. Most importantly, we found that hens with the derived BCO2 genotype were capable of allocating stored carotenoids to their eggs, suggesting a functional benefit through buffering any shortage in the diet during egg production. Nevertheless, it is of interest that loss of function mutations in BCO2 gene are prevalent in other domesticates including cows, rabbits, and sheep, and, given the importance of carotenoids in development, reproduction, and immunity, it is possible that derived BCO2 alleles may provide a general mechanism in multiple domestic species to deal with higher demand for carotenoids in an environment with carotenoid shortage in the diet.
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| 8. |
- Karlsson, Anna-Carin, et al.
(författare)
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The effect of a domestication related mutation in the thyroid stimulating hormone receptor (TSHR) on photoperiodic response and reproduction in chicken
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The thyroid stimulating hormone receptor (TSHR) has been suggested to be a “domestication locus” in the chicken. A strong selective sweep over the gene in domestic breeds of chicken, but not in the ancestral Red Junglefowl, and significant effects of a mutation in TSHR on domestication related traits in chicken, indicate that the gene has been important for the chicken domestication. The TSHR play a key role in the signal transduction of seasonal reproduction, which is characteristically less strict in domestic animals. We investigated the effect of the mutation on reproductive traits as well as TSHB, TSHR, DIO2 and DIO3 gene expression during altered day length (photoperiod) in females and males intercross chickens homozygous for the mutation (d/d) or wild type homozygotes (w/w). This allowed an assessment of the effect of genotype at this locus against a random mix of RJF and WL genotypes throughout the rest of the genome. The TSHR gene expression was significantly lower in both d/d females and males, in comparison to w/w individuals, indicating a strong effect of the “domestic” mutation on gene expression. The d/d females showed a faster increase in the onset of laying than w/w females, and d/d males showed a reduced response to altered day length in testicular size and significant lower levels of TSHB and DIO3 expression, in comparison to w/w males. Additionally, pure White Leghorn females kept under natural day length in Sweden during December showed active ovaries and significant lower levels of TSHR and DIO3 expression in comparison to Red Junglefowl females kept under similar conditions. Our study suggest that the TSHR mutation affects photoperiodic response in chicken in the direction of being less dependent on seasonal reproduction, a typical domestication feature, and may therefore have been important for the chicken domestication.
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| 9. |
- Løtvedt, Pia, 1987-, et al.
(författare)
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Chicken domestication changes expression of stress-related genes in brain, pituitary and adrenals
- 2017
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Ingår i: Neurobiology of stress. - : Elsevier. - 2352-2895. ; 7, s. 113-121
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Tidskriftsartikel (refereegranskat)abstract
- Domesticated species have an attenuated behavioral and physiological stress response compared to their wild counterparts, but the genetic mechanisms underlying this change are not fully understood. We investigated gene expression of a panel of stress response-related genes in five tissues known for their involvement in the stress response: hippocampus, hypothalamus, pituitary, adrenal glands and liver of domesticated White Leghorn chickens and compared it with the wild ancestor of all domesticated breeds, the Red Junglefowl. Gene expression was measured both at baseline and after 45 min of restraint stress. Most of the changes in gene expression related to stress were similar to mammals, with an upregulation of genes such as FKBP5, C-FOS and EGR1 in hippocampus and hypothalamus and StAR, MC2R and TH in adrenal glands. We also found a decrease in the expression of CRHR1 in the pituitary of chickens after stress, which could be involved in negative feedback regulation of the stress response. Furthermore, we observed a downregulation of EGR1 and C-FOS in the pituitary following stress, which could be a potential link between stress and its effects on reproduction and growth in chickens. We also found changes in the expression of important genes between breeds such as GR in the hypothalamus, POMC and PC1 in the pituitary and CYP11A1 and HSD3B2 in the adrenal glands. These results suggest that the domesticated White Leghorn may have a higher capacity for negative feedback of the HPA axis, a lower capacity for synthesis of ACTH in the pituitary and a reduced synthesis rate of corticosterone in the adrenal glands compared to Red Junglefowl. All of these findings could explain the attenuated stress response in the domesticated birds.
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| 10. |
- Warnefors, Maria, et al.
(författare)
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Sex-biased microRNA expression in mammals and birds reveals underlying regulatory mechanisms and a role in dosage compensation
- 2017
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Ingår i: Genome Research. - : COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT. - 1088-9051 .- 1549-5469. ; 27:12, s. 1961-1973
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Tidskriftsartikel (refereegranskat)abstract
- Sexual dimorphism depends on sex-biased gene expression, but the contributions of microRNAs (miRNAs) have not been globally assessed. We therefore produced an extensive small RNA sequencing data set to analyze male and female miRNA expression profiles in mouse, opossum, and chicken. Our analyses uncovered numerous cases of somatic sex-biased miRNA expression, with the largest proportion found in the mouse heart and liver. Sex-biased expression is explained by miRNA-specific regulation, including sex-biased chromatin accessibility at promoters, rather than piggybacking of intronic miRNAs on sex-biased protein-coding genes. In mouse, but not opossum and chicken, sex bias is coordinated across tissues such that autosomal testis-biased miRNAs tend to be somatically male-biased, whereas autosomal ovary-biased miRNAs are female-biased, possibly due to broad hormonal control. In chicken, which has a Z/W sex chromosome system, expression output of genes on the Z Chromosome is expected to be male-biased, since there is no global dosage compensation mechanism that restores expression in ZW females after almost all genes on the W Chromosome decayed. Nevertheless, we found that the dominant liver miRNA, miR-122-5p, is Z-linked but expressed in an unbiased manner, due to the unusual retention of a W-linked copy. Another Z-linked miRNA, the male-biased miR-2954-3p, shows conserved preference for dosage-sensitive genes on the Z Chromosome, based on computational and experimental data from chicken and zebra finch, and acts to equalize male-to-female expression ratios of its targets. Unexpectedly, our findings thus establish miRNA regulation as a novel gene-specific dosage compensation mechanism.
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