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Whole genome resequencing reveals loci under selection during chicken domestication
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2010 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 464, no 7288, 587-591 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2010. Vol. 464, no 7288, 587-591 p.
National Category
Genetics
Research subject
Genetics
Identifiers
URN: urn:nbn:se:uu:diva-108259DOI: 10.1038/nature08832ISI: 000275974200047PubMedID: 20220755OAI: oai:DiVA.org:uu-108259DiVA: diva2:234779
Available from: 2009-09-10 Created: 2009-09-10 Last updated: 2016-05-18
In thesis
1. Investigation of Mechanics of Mutation and Selection by Comparative Sequencing
Open this publication in new window or tab >>Investigation of Mechanics of Mutation and Selection by Comparative Sequencing
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The process of evolution is of both scientific and medical interest. This thesis presents several studies using complete genomic reference sequences, comparative genomic data, and intraspecific diversity data to study the two key processes of evolution: mutation and selection.

Large duplications, deletions, inversions, and translocations of DNA contribute to genomic variation both between and within species. Human chromosomes 15 and 17 contain a high percentage of dispersed, recently duplicated sequences. Examination of the relationships between these sequences showed that the majority of all duplications within each chromosome could be linked through core sequences that are prone to duplication. Comparison to orthologous sequences in other mammals allowed a reconstruction of the ancestral state of the human chromosomes, revealing that regions of rearrangement specific to the human lineage are highly enriched in chromosome-specific duplications. Comparison to copy number variation data from other studies also shows that these regions are enriched in current human structural variation. One specific region, the MAPT locus at 17q21.31, known to contain an inversion polymorphism in Europeans, was resequenced completely across both human orientation haplotypes and in chimpanzee and orangutan, revealing complex duplication structures at the inversion breakpoints, with the human region being more complex than chimpanzee or orangutan. Fluorescent in-situ hybridization analysis of human, chimpanzee, and orangutan chromosomes showed inversion polymorphisms of independent origin in all three species, demonstrating that this region has been a hotspot of genomic rearrangement for at least twelve million years. These results reveal a mechanistic relationship between sequence duplication and rearrangement in the great apes.

We also generated a draft sequence of the chimpanzee genome and compared it to that of the human. Among other findings, this showed that CpG dinucleotides contribute 25% of all single base mutations, with a rate of mutation ~10-fold that of other bases, and that the male mutation rate in great apes is ~5-6 times the female rate, a higher ratio than had been observed in comparisons of primates and rodents. We detected six regions of probable recent positive selection in humans with a statistical method relying on chimpanzee sequence to control for regional variation in mutation rates.

Finally, resequencing of several lines of domestic chicken and comparison to the reference chicken genome identified a number of gene deletions fixed in domestic lines and also several potential selective sweeps. Of particular interest are a missense mutation in TSHR nearly fixed in all domestic chickens and a partial deletion of SH3RF2 fixed in a high growth line. The TSHR mutation may play a role in relaxation of seasonal reproduction. A high-resolution QTL mapping experiment showed that the SH3RF2 deletion is significantly associated with increased growth.

This work provides important new insights into the mechanics of evolutionary change at both the single nucleotide and structural level and identifies potential targets of natural and artificial selection in humans and chickens.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 63 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 482
Keyword
chicken, chimpanzee, human, evolution, segmental duplication, structural variation, chromosomal rearrangement, comparative genomics, positive selection, selective sweep
National Category
Genetics
Research subject
Genetics
Identifiers
urn:nbn:se:uu:diva-108266 (URN)978-91-554-7604-5 (ISBN)
Public defence
2009-10-23, C8:305, BMC, Husargatan 3, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2009-10-01 Created: 2009-09-10 Last updated: 2009-10-01
2. Genetic and Genomic Studies in Chicken: Assigning Function to Vertebrate Genes
Open this publication in new window or tab >>Genetic and Genomic Studies in Chicken: Assigning Function to Vertebrate Genes
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A major challenge in the post-genomic era is to understand how genome sequence variants (genotype) give rise to the enormous diversity observed in terms of morphology, physiology and behavior (phenotype) among living organisms. Domestic animals—with their tremendous phenotypic variation—are excellent model organisms for determining the relationships between genotype and phenotype. In this thesis, I describe the utilization of the chicken, in combination with modern genetic and genomic approaches, in developing our understanding of the genetic mechanisms underlying phenotypic variation. These studies provide novel information on the genetics behind variation in carotenoid- and melanin-based pigmentation—observed in many organisms—and also cast light on the genetic basis of chicken domestication.

In paper I, we report that the yellow skin phenotype—observed in most commercial chickens—is caused by one or several tissue-specific mutations altering the expression of beta-carotene oxygenase 2 (BCO2 or BCDO2) in skin. In addition, we present the first conclusive evidence of a hybrid origin of the domestic chicken, since the allele causing yellow skin most likely originates from the grey jungle fowl (Gallus sonneratii) and not from the previously described sole ancestor, the red jungle fowl (Gallus gallus).

In paper II, we detect a number of loci that were likely important during the domestication process of chicken and the later specialization into meat (broiler) and egg (layer) producing lines. One of the major findings was that worldwide, almost all domestic chickens carry a missense mutation in TSHR (thyroid stimulating hormone receptor) in a position that is completely conserved amongst vertebrates. We speculate that this “domestication-mutation” has played an important role in the transformation of the wild red jungle fowl ancestor into the modern domestic chicken.

In paper III, we demonstrate that the dilution of red (pheomelanin) pigmentation—observed in the plumage of the Inhibitor of Gold chicken—is caused by a frame-shift mutation in the catechol-O-methyltransferase domain containing 1 (COMTD1) gene. The production and regulation of pheomelanin is poorly understood and this discovery advances our current knowledge of this pathway.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 56 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 732
Keyword
Chicken, BCO2, TSHR, COMTD1, Phenotypic variation, Domestication, Selective sweeps, Pigmentation
National Category
Medical and Health Sciences
Research subject
Molecular Genetics
Identifiers
urn:nbn:se:uu:diva-162597 (URN)978-91-554-8246-6 (ISBN)
Public defence
2012-02-03, B42, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2012-01-13 Created: 2011-12-01 Last updated: 2012-01-16Bibliographically approved

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