Award details

Understanding the Retention of Genes Following Duplication

Reference	BB/I020489/1
Principal Investigator / Supervisor	Professor Simon Lovell
Co-Investigators / Co-Supervisors	Professor Daniela Delneri, Professor David Robertson
Institution	The University of Manchester
Department	Life Sciences
Funding type	Research
Value (£)	554,131
Status	Completed
Type	Research Grant
Start date	03/01/2012
End date	02/01/2015
Duration	36 months

Abstract

We propose a multidisciplinary study to investigate the phenotypic consequences of gene duplication, and the subsequent evolution of duplicate genes. For this research we will use the yeast Saccharomyces cerevisiae. The key aspect of this proposal is the combination of hypothesis generation using bioinformatic analysis of biological systems in yeast, coupled with experimental testing of these hypotheses. We will computationally model various systems, and predict the likely effects of gene duplication on protein interaction networks, metabolic networks, protein complexes and a range of other systems. Based on these predictions we will make 'artificial duplicates' by knocking-in extra copies of genes. We will measure the fitness of these strains carrying extra copies of genes, thereby determining the accuracy of our predictions and adding to our knowledge of the various systems involved. We will also determine the relationship between fitness of the duplicate-bearing strains and the probability that the new duplicates will be lost from the genome. In addition, this work will be supplemented by the computational analysis of changes in protein-coding regions that have recently been duplicated. Such changes can be an indication of functional innovation. Finally, we will attempt to alter the probability of gene loss by changing the complement of genes knocked in, by adding genes to a cassette that will provide positive balancing fitness, and by altering the growth conditions to promote gene retention. In this way we will, for the first time, be able to study the immediate functional effects of gene duplication, and evolutionary dynamics of duplicated genes.

Summary

The genome is in a state of constant flux, with genes being added and lost continually over evolutionary time. Recent genome sequencing projects of populations suggest that the numbers of copies of many genes vary between individuals. When we study organisms such as yeast, we also see large differences in the numbers of copies of genes within a species. This suggests that duplication of genes is the major source of new genetic material, innovation of biological function, and the complexity of organisms. Moreover, duplication appears to be a key mechanism by which organisms can adapt to their environments. Gain and loss of genes are the two ways in which the genetic content can differ within one species and between species. By looking at the genomes of existing species we can attempt to reconstruct the evolutionary history. However, these studies can miss some of the immediate events, such as a gene being duplicated and then lost. In this project we will make artificial copies of genes in yeast, and determine how this affects how they grow under different conditions. We predict that many gene duplications will be advantageous, whereas others will be deleterious, but this may differ according to the conditions under which the yeast are grown. We will also grow the yeast strains that contain the duplicates for long periods of time in the lab, and determine whether they have lost the genes we previously duplicated. We will also study closely-related species to see whether there is functional innovation in duplicated genes. We will be able to study the immediate functional effects of gene duplication, and also the immediate evolutionary events. We will therefore be able to study the 'cutting edge' of evolutionary change. This work will provide a new understanding of how an organisms set of genes can adapt to new environments, and how complex biological systems evolve.

Impact Summary

The impact of this research will be felt by: 1. Biotechnology companies, and in particular, developing synthetic biology companies. As outlined in the 'academic beneficiaries' section, this project has clear applications to synthetic biology. Specifically, knowledge of the rates of gene loss, and interventions that may be made to prevent gene loss are important precursors to manipulating organisms for technological ends. Synthetic biology is a new approach that has not yet been widely explored by biotechnology companies. However, this situation is likely to change in the near future. Our research will therefore have broad impact to this developing commercial area. 2. The broader public. There is a widespread public interest in evolution, but also a general wariness with regard to engineering of organisms. It is therefore important that we continue with, and expand, our ongoing efforts for public engagement.

Committee	Research Committee D (Molecules, cells and industrial biotechnology)
Research Topics	Microbiology
Research Priority	Systems Approach to Biological research
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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