Award details

Development of codon-based substitution models for detecting natural selection in protein-coding genes

Reference	BB/C512329/1
Principal Investigator / Supervisor	Professor Ziheng Yang
Co-Investigators / Co-Supervisors
Institution	University College London
Department	Genetics Evolution and Environment
Funding type	Research
Value (£)	225,528
Status	Completed
Type	Research Grant
Start date	05/07/2005
End date	04/02/2009
Duration	43 months

Abstract

Codon-based evolutionary models have been widely used in comparative analysis of protein-coding DNA sequences and provide a powerful framework for functional interpretation of genomic data. The widespread use also revealed weakness in current implementations. In this project we will extend and develop models of codon substitution to detect the effects of positive and purifying natural selection using sequences from different species and from closely related species. Our early methods for detecting positive selection affecting a subset of amino acid sites throughout the phylogenetic tree (the site models) or affecting a subset of sites along particular branches of interest (the branch-site models) have been implemented using the so-called naive Empirical Bayes method and do not account for sampling errors in the parameter estimates, which may be unreliable in small datasets. We will develop powerful statistical methods and efficient computational algorithms to accommodate the uncertainties in the parameters to improve the accuracy of the inference procedure. Computer simulation will be used to examine the accuracy and power of the new methods. The improved methods will be used in comparative genomics analysis to detect genes under positive selection and to test theories of molecular evolution and gene duplication. We will develop codon-based mutation models that explicitly describe the effect of natural selection at silent sites and use Drosophila and yeast genomic datasets to test their utilities.

Summary

unavailable

Committee	Closed Committee - Genes & Developmental Biology (GDB)
Research Topics	Microbiology, Technology and Methods Development
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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