Martin Johnsson

Heritable genome-wide variation of gene expression and promoter methylation between wild and domesticated chickens

BackgroundVariations in gene expression, mediated by epigenetic mechanisms, may cause broad phenotypic effects in animals. However, it has been debated to what extent expression variation and epigenetic modifications, such as patterns of DNA methylation, are transferred across generations, and therefore it is uncertain what role epigenetic variation may play in adaptation.ResultsIn Red Junglefowl, ancestor of domestic chickens, gene expression and methylation profiles in thalamus/hypothalamus differed substantially from that of a domesticated egg laying breed. Expression as well as methylation differences were largely maintained in the offspring, demonstrating reliable inheritance of epigenetic variation. Some of the inherited methylation differences were tissue-specific, and the differential methylation at specific loci were little changed after eight generations of intercrossing between Red Junglefowl and domesticated laying hens. There was an over-representation of differentially expressed and methylated genes in selective sweep regions associated with chicken domestication.ConclusionsOur results show that epigenetic variation is inherited in chickens, and we suggest that selection of favourable epigenomes, either by selection of genotypes affecting epigenetic states, or by selection of methylation states which are inherited independently of sequence differences, may have been an important aspect of chicken domestication.

A Sexual Ornament in Chickens Is Affected by Pleiotropic Alleles at HAO1 and BMP2, Selected during Domestication

Domestication is one of the strongest forms of short-term, directional selection. Although selection is typically only exerted on one or a few target traits, domestication can lead to numerous changes in many seemingly unrelated phenotypes. It is unknown whether such correlated responses are due to pleiotropy or linkage between separate genetic architectures. Using three separate intercrosses between wild and domestic chickens, a locus affecting comb mass (a sexual ornament in the chicken) and several fitness traits (primarily medullary bone allocation and fecundity) was identified. This locus contains two tightly-linked genes, BMP2 and HAO1, which together produce the range of pleiotropic effects seen. This study demonstrates the importance of pleiotropy (or extremely close linkage) in domestication. The nature of this pleiotropy also provides insights into how this sexual ornament could be maintained in wild populations.

Domestication Effects on Stress Induced Steroid Secretion and Adrenal Gene Expression in Chickens.

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.

Genetical Genomics of Behavior: A Novel Chicken Genomic Model for Anxiety Behavior

The identification of genetic variants responsible for behavioral variation is an enduring goal in biology, with wide-scale ramifications, ranging from medical research to evolutionary theory on personality syndromes. Here, we use for the first time a large-scale genetical genomics analysis in the brains of chickens to identify genes affecting anxiety as measured by an open field test. We combine quantitative trait locus (QTL) analysis in 572 individuals and expression QTL (eQTL) analysis in 129 individuals from an advanced intercross between domestic chickens and Red Junglefowl. We identify 10 putative quantitative trait genes affecting anxiety behavior. These genes were tested for an association in the mouse Heterogeneous Stock anxiety (open field) data set and human GWAS data sets for bipolar disorder, major depressive disorder, and schizophrenia. Although comparisons between species are complex, associations were observed for four of the candidate genes in mice and three of the candidate genes in humans. Using a multimodel approach we have therefore identified a number of putative quantitative trait genes affecting anxiety behavior, principally in chickens but also with some potentially translational effects as well. This study demonstrates that chickens are an excellent model organism for the genetic dissection of behavior.

The role of pleiotropy and linkage in genes affecting a sexual ornament and bone allocation in the chicken

Sexual selection and the ornaments that inform such choices have been extensively studied, particularly from a phenotypic perspective. Although more is being revealed about the genetic architecture of sexual ornaments, much still remains to be discovered. The comb of the chicken is one of the most widely recognized sexual ornaments, which has been shown to be correlated with both fecundity and bone allocation. In this study, we use a combination of multiple intercrosses between White Leghorn populations and wild‐derived Red Junglefowl to, first, map quantitative trait loci (QTL) for bone allocation and, second, to identify expression QTL that correlate and colocalize with comb mass. These candidate quantitative genes were then assessed for potential pleiotropic effects on bone tissue and fecundity traits. We identify genes that correlate with both relative comb mass and bone traits suggesting a combination of both pleiotropy and linkage mediates gene regulatory variation in these traits.

Genetic regulation of bone metabolism in the chicken: similarities and differences to Mammalian systems.

Birds have a unique bone physiology, due to the demands placed on them through egg production. In particular their medullary bone serves as a source of calcium for eggshell production during lay and undergoes continuous and rapid remodelling. We take advantage of the fact that bone traits have diverged massively during chicken domestication to map the genetic basis of bone metabolism in the chicken. We performed a quantitative trait locus (QTL) and expression QTL (eQTL) mapping study in an advanced intercross based on Red Junglefowl (the wild progenitor of the modern domestic chicken) and White Leghorn chickens. We measured femoral bone traits in 456 chickens by peripheral computerised tomography and femoral gene expression in a subset of 125 females from the cross with microarrays. This resulted in 25 loci for female bone traits, 26 loci for male bone traits and 6318 local eQTL loci. We then overlapped bone and gene expression loci, before checking for an association between gene expression and trait values to identify candidate quantitative trait genes for bone traits. A handful of our candidates have been previously associated with bone traits in mice, but our results also implicate unexpected and largely unknown genes in bone metabolism. In summary, by utilising the unique bone metabolism of an avian species, we have identified a number of candidate genes affecting bone allocation and metabolism. These findings can have ramifications not only for the understanding of bone metabolism genetics in general, but could also be used as a potential model for osteoporosis as well as revealing new aspects of vertebrate bone regulation or features that distinguish avian and mammalian bone.

The domesticated brain : genetics of brain mass and brain structure in an avian species.

As brain size usually increases with body size it has been assumed that the two are tightly constrained and evolutionary studies have therefore often been based on relative brain size (i.e. brain size proportional to body size) rather than absolute brain size. The process of domestication offers an excellent opportunity to disentangle the linkage between body and brain mass due to the extreme selection for increased body mass that has occurred. By breeding an intercross between domestic chicken and their wild progenitor, we address this relationship by simultaneously mapping the genes that control inter-population variation in brain mass and body mass. Loci controlling variation in brain mass and body mass have separate genetic architectures and are therefore not directly constrained. Genetic mapping of brain regions indicates that domestication has led to a larger body mass and to a lesser extent a larger absolute brain mass in chickens, mainly due to enlargement of the cerebellum. Domestication has traditionally been linked to brain mass regression, based on measurements of relative brain mass, which confounds the large body mass augmentation due to domestication. Our results refute this concept in the chicken.

Domestication and tameness: brain gene expression in red junglefowl selected for less fear of humans suggests effects on reproduction and immunology.

The domestication of animals has generated a set of phenotypic modifications, affecting behaviour, appearance, physiology and reproduction, which are consistent across a range of species. We hypothesized that some of these phenotypes could have evolved because of genetic correlation to tameness, an essential trait for successful domestication. Starting from an outbred population of red junglefowl, ancestor of all domestic chickens, we selected birds for either high or low fear of humans for five generations. Birds from the fifth selected generation (S5) showed a divergent pattern of growth and reproduction, where low fear chickens grew larger and produced larger offspring. To examine underlying genetic mechanisms, we used microarrays to study gene expression in thalamus/hypothalamus, a brain region involved in fear and stress, in both the parental generation and the S5. While parents of the selection lines did not show any differentially expressed genes, there were a total of 33 genes with adjusted p-values below 0.1 in S5. These were mainly related to sperm-function, immunological functions, with only a few known to be relevant to behaviour. Hence, five generations of divergent selection for fear of humans produced changes in hypothalamic gene expression profiles related to pathways associated with male reproduction and to immunology. This may be linked to the effects seen on growth and size of offspring. These results support the hypothesis that domesticated phenotypes may evolve because of correlated effects related to reduced fear of humans.

Similar recent selection criteria associated with different behavioural effects in two dog breeds.

Selection during the last decades has split some established dog breeds into morphologically and behaviourally divergent types. These breed splits are interesting models for behaviour genetics since selection has often been for few and well‐defined behavioural traits. The aim of this study was to explore behavioural differences between selection lines in golden and Labrador retriever, in both of which a split between a common type (pet and conformation) and a field type (hunting) has occurred. We hypothesized that the behavioural profiles of the types would be similar in both breeds. Pedigree data and results from a standardized behavioural test from 902 goldens (698 common and 204 field) and 1672 Labradors (1023 and 649) were analysed. Principal component analysis revealed six behavioural components: curiosity, play interest, chase proneness, social curiosity, social greeting and threat display. Breed and type affected all components, but interestingly there was an interaction between breed and type for most components. For example, in Labradors the common type had higher curiosity than the field type (F1,1668 = 18.359; P < 0.001), while the opposite was found in goldens (F1,897 = 65.201; P < 0.001). Heritability estimates showed considerable genetic contributions to the behavioural variations in both breeds, but different heritabilities between the types within breeds was also found, suggesting different selection pressures. In conclusion, in spite of similar genetic origin and similar recent selection criteria, types behave differently in the breeds. This suggests that the genetic architecture related to behaviour differs between the breeds.

Feralisation targets different genomic loci to domestication in the chicken

Feralisation occurs when a domestic population recolonizes the wild, escaping its previous restricted environment, and has been considered as the reverse of domestication. We have previously shown that Kauai Islands feral chickens are a highly variable and admixed population. Here we map selective sweeps in feral Kauai chickens using whole-genome sequencing. The detected sweeps were mostly unique to feralisation and distinct to those selected for during domestication. To ascribe potential phenotypic functions to these genes we utilize a laboratory-controlled equivalent to the Kauai population—an advanced intercross between Red Junglefowl and domestic layer birds that has been used previously for both QTL and expression QTL studies. Certain sweep genes exhibit significant correlations with comb mass, maternal brooding behaviour and fecundity. Our analyses indicate that adaptations to feral and domestic environments involve different genomic regions and feral chickens show some evidence of adaptation at genes associated with sexual selection and reproduction.