Domestic animals are excellent models for genetic studies of phenotypic evolution. They have evolved genetic adaptations to a new environment, the farm, and have been subjected to strong human-driven selection leading to remarkable phenotypic changes in morphology, physiology and behaviour. Identifying the genetic changes underlying these developments provides new insight into general mechanisms by which genetic variation shapes phenotypic diversity. Here we describe the use of massively parallel sequencing to identify selective sweeps of favourable alleles and candidate mutations that have had a prominent role in the domestication of chickens (Gallus gallus domesticus) and their subsequent specialization into broiler (meat-producing) and layer (egg-producing) chickens. We have generated 44.5-fold coverage of the chicken genome using pools of genomic DNA representing eight different populations of domestic chickens as well as red jungle fowl (Gallus gallus), the major wild ancestor. We report more than 7,000,000 single nucleotide polymorphisms, almost 1,300 deletions and a number of putative selective sweeps. One of the most striking selective sweeps found in all domestic chickens occurred at the locus for thyroid stimulating hormone receptor (TSHR), which has a pivotal role in metabolic regulation and photoperiod control of reproduction in vertebrates. Several of the selective sweeps detected in broilers overlapped genes associated with growth, appetite and metabolic regulation. We found little evidence that selection for loss-of-function mutations had a prominent role in chicken domestication, but we detected two deletions in coding sequences that we suggest are functionally important. This study has direct application to animal breeding and enhances the importance of the domestic chicken as a model organism for biomedical research.

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Domestication of wild boar (Sus scrofa) and subsequent selection have resulted in dramatic phenotypic changes in domestic pigs for a number of traits, including behavior, body composition, reproduction, and coat color. Here we have used whole-genome resequencing to reveal some of the loci that underlie phenotypic evolution in European domestic pigs. Selective sweep analyses revealed strong signatures of selection at three loci harboring quantitative trait loci that explain a considerable part of one of the most characteristic morphological changes in the domestic pig-the elongation of the back and an increased number of vertebrae. The three loci were associated with the NR6A1, PLAG1, and LCORL genes. The latter two have repeatedly been associated with loci controlling stature in other domestic animals and in humans. Most European domestic pigs are homozygous for the same haplotype at these three loci. We found an excess of derived nonsynonymous substitutions in domestic pigs, most likely reflecting both positive selection and relaxed purifying selection after domestication. Our analysis of structural variation revealed four duplications at the KIT locus that were exclusively present in white or white-spotted pigs, carrying the Dominant white, Patch, or Belt alleles. This discovery illustrates how structural changes have contributed to rapid phenotypic evolution in domestic animals and how alleles in domestic animals may evolve by the accumulation of multiple causative mutations as a response to strong directional selection.

Interaction between genes, or epistasis, is found to be common and it is a key concept for understanding adaptation and evolution of natural populations, response to selection in breeding programs, and determination of complex disease. Currently, two independent classes of models are used to study epistasis. Statistical models focus on maintaining desired statistical properties for detection and estimation of genetic effects and for the decomposition of genetic variance using average effects of allele substitutions in populations as parameters. Functional models focus on the evolutionary consequences of the attributes of the genotype-phenotype map using natural effects of allele substitutions as parameters. Here we provide a new, general and unified model framework: the natural and orthogonal interactions (NOIA) model. NOIA implements tools for transforming genetic effects measured in one population to the ones of other populations (e.g., between two experimental designs for QTL) and parameters of statistical and functional epistasis into each other (thus enabling us to obtain functional estimates of QTL), as demonstrated numerically. We develop graphical interpretations of functional and statistical models as regressions of the genotypic values on the gene content, which illustrates the difference between the models-the constraint on the slope of the functional regression-and when the models are equivalent. Furthermore, we use our theoretical foundations to conceptually clarify functional and statistical epistasis, discuss the advantages of NOIA over previous theory, and stress the importance of linking functional and statistical models.

It is an enigma how long-term selection in model organisms and agricultural species can lead to marked phenotypic changes without exhausting genetic variation for the selected trait. Here, we show that the genetic architecture of an apparently major locus for growth in chicken dissects into a genetic network of four interacting loci. The interactions in this radial network mediate a considerably larger selection response than predicted by a single-locus model.