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  Understanding evolutionary adaptation in the mammalian genome


   School of Biological Sciences

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Prof P Keightley  No more applications being accepted  Competition Funded PhD Project (UK Students Only)

About the Project

Deadline 20 May - interested individuals should email [Email Address Removed] directly. Send a two page Curriculum Vitae including contact details for two academic referees; a one page statement of research interests and grades/transcript of marks.

My lab works on fundamental questions in evolutionary biology, centred on the theme of the genetic basis of evolutionary change. Our research is now being revolutionized by the availability of complete genome sequences from multiple individuals of the same species sampled from natural populations. These new data will help us to answer several hotly debated, open questions in evolutionary biology, including the following: 1. Does most adaptive evolution involve changes in the sequences of proteins, or does most adaptation result from regulatory changes affecting the timing and tissue-specificity of gene expression? 2. Do species with different population sizes show different signatures of natural selection in their genomes? In our lab, we are addressing questions like these, using whole-genome sequences of multiple individuals from several mammalian species generated within our lab or obtained from the public archive.

A PhD project is available to work in this general area. The project details will be worked out following discussion between the student, supervisor and Keightley lab members. The project could address a range of questions, including the following:

• How does nucleotide change between species in protein-coding genes or regulatory elements relate to within-species nucleotide diversity at linked sites? What does this relationship tell us about the strength and frequency of natural selection acting on coding versus regulatory sequences?

• We have generated genome sequences from multiple individuals of wild rodent species, including the house mouse (Mus musculus castaneus) and the brown rat (Rattus norvegicus), sampled from the species’ ancestral ranges in NW India and NE China, respectively. Initial analysis suggests that the effective population size of the brown rat is intermediate between that of humans and house mice, leading to predictable differences between these species in patterns of nucleotide diversity and the frequency of adaptive molecular evolution. Are these differences revealed in a genome-wide analysis and what do the results tell us about the strength of natural selection acting in coding and noncoding DNA?

The project will provide training and experience in evolutionary genetics research, the analysis of next-generation sequence data and computational biology to tackle some of the most fundamental open questions in evolutionary biology.

See lab website: http://homepages.ed.ac.uk/eang33/

Funding Notes

This opportunity is only open to UK nationals (or EU students who have been resident in the UK for 3+ years) due to restrictions imposed by the funding body.


References

Halligan, D. L., Oliver, F., Eyre-Walker, A., Harr, B. and Keightley, P. D. (2010). Evidence for pervasive adaptive protein evolution in wild mice. PLoS Genetics 6: e1000825.

Halligan, D. L., Oliver, F., Guthrie, J., Stemshorn, K. C., Harr, B. and Keightley, P. D. (2011). Positive and negative selection in murine ultra-conserved noncoding elements. Molecular Biology and Evolution 28: 2651-2660.


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