Interested individuals must follow the "how to apply" link on the Geosciences E4 Doctoral Training Partnership web page: http://www.ed.ac.uk/e4-dtp/how-to-apply
Summary
This project will investigate the genetic basis and selection of immune responses in the Soay sheep of St Kilda, integrating traditional ecological approaches with cutting-edge sequencing technology.
Project background
Immune responses can have a large impact on an individual’s condition, disease resistance, survival and reproduction and are likely to be under strong selection in the wild. Evolutionary theory predicts that strong selection should erode the underlying genetic variation of traits. Yet, immune responses are highly variable in wild populations. If we can determine the genetic basis of immune responses (e.g. the number and effect sizes of underlying genes), we can begin to understand how they evolve over different evolutionary timescales.
This PhD will investigate the genetic causes and evolutionary consequences of immune trait variation in a wild population. Soay sheep (Ovis aries) are a primitive breed of domestic sheep that have lived wild on the St Kilda archipelago since the Bronze Age. Soay sheep are naturally infected with strongyle nematodes, with genetic effects explaining up to 50% of the observed variation. Recently, a genome-wide association study (GWAS) with ~40,000 SNP markers found regions of the genome associated with anti-strongyleantibody expression (IgA, IgE and IgG), including a genomic region with a very large effect on IgA levels. However, it is not known if and how the genes identified are associated with differences in condition, reproduction and survival, and how this may differ at different life stages. The aim of this PhD project is to use whole genome-sequencing techniques to better map the loci associated with IgA, IgE, and IgG variation, and to investigate the evolutionary mechanisms explaining why substantial genetic variation persists in this population.
Research questions
- What new loci and candidate mutations for immune trait variation can we identify using whole-genome sequence data?
- Are genetic variants associated with condition, reproduction and survival?
- Do these associations vary with life-stage, sex and/or over time?
- Have any immune loci introgressed from modern breeds?
- What are the long-term signatures of selection at immune loci?
Methodology
The Soay sheep of St Kilda have been subject to a long-term study since 1985. Currently, we have phenotype, life-history and pedigree information for >8,000 individuals genotyped at ~415,000 genome-wide SNP loci. The student will integrate this data with newly obtained whole genome sequence (WGS) information to address the research questions above.
Year 1: Imputation of WGS data to 7000 sheep and conducting genome-wide association studies to identify candidate causal mutations. The analysis will be also stratified by age and sex to investigate variation in genetic architectures between classes.
Year 2: Investigating selection at immune loci by investigating the association between causal variants and individual condition, survival and reproduction using both single locus and genomic prediction-based approaches.
Year 3: Investigation of evolutionary history and historical signatures of selection on immune loci, and identifying potential molecular mechanisms associated with phenotypic variation.
The student will be encouraged to contribute to fieldwork on St Kilda to collect samples and aid the field team to learn about the ecology of the system.
Training
A comprehensive training programme will be provided comprising both specialist scientific training and generic transferable and professional skills. The supervisors will provide cutting-edge training in quantitative genetics, evolutionary genomics, statistics and bioinformatics. The first year will include an intensive one-semester course on population genetics, quantitative genetics and statistics at the Institute of Ecology and Evolution which will provide a basis for the analytical work. Further training will be provided by NERC E4 workshops/symposia and Edinburgh Genomics coding and bioinformatics courses. The student will also be able to take advantage of national and international collaborative links of the supervisors in the experimental, livestock and wild genomics communities.
Requirements
Candidates must be highly motivated with a keen interest in evolutionary biology and genetics. The project will be mostly computational and will suit students with some coding experience (e.g. R, Python, or similar) and those who are willing to learn.
www.sejohnston.com
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