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Evolution of recombination from a retroviral perspective: Mathematical models and data analysis

English title Evolution of recombination from a retroviral perspective: Mathematical models and data analysis
Applicant Bonhoeffer Sebastian
Number 116408
Funding scheme Project funding
Research institution Gruppe Theoretische Biologie Departement Umweltsystemwissenschaften ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Ecology
Start/End 01.01.2008 - 31.12.2010
Approved amount 755'000.00
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All Disciplines (2)

Discipline
Ecology
Experimental Microbiology

Keywords (6)

mathematical modelling; population dynamics; population genetics; retroviruses/HIV; evolution of recombination; evolution of drug resistance

Lay Summary (English)

Lead
Lay summary
Retroviruses are unique among animal viruses in that two full-length genomic RNA molecules are packaged into each virion. In case that both genomes are genetically distinct, template switching between both genomic strands during reverse transcription can lead to recombination. Retroviruses are thus capable of a simple form of sexual reproduction. This research proposal is divided into 3 projects. The primary aim of the first project is to investigate retroviral recombination as a means to test and further develop theories on the evolutionary benefit of sexual reproduction, here defined broadly as reproductive strategies that involve shuffling of the parental genetic material. Although many theories have been put forward, a satisfactory explanation of the evolutionary benefit of sexual reproduction remains elusive, because most theories require very restricted conditions, are hard to test experimentally, and lack supporting data. The aim of the second project is to investigate the consequences of recombination for the evolution of drug resistance in HIV-1.In particular, we plan to investigate (i) how drug resistance mutations interact to determine fitness, (ii) how these interactions change in the presence of different drugs, and (iii) whether the nature of these interactions is associated with protein structure or drug class. Thr third project investigates fitness effects of mutations rather than interactions between mutations and thus does not directly address recombination.The proposal addresses important questions of both basic and applied science. A better understanding of the forces selecting for recombination in retroviruses will shed light onto one of the most important open questions of evolutionary biology, namely the evolution of sexual reproduction. In particular the first project may shed new light on this question by developing a better understanding of the factors that govern the evolution of recombination in retroviruses. As viruses are more amenable to experimentation than higher organisms, our work may furthermore help to develop testable theories for the evolution of sexual reproduction. On the other hand a better understanding of the nature of the fitness effects and fitness interactions will also help to elucidate mutational pathways to drug resistance and may thus help in the longer term to design therapies that are less prone to failure due to resistance.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

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Associated projects

Number Title Start Funding scheme
133129 Evolutionary genetics of HIV-1: Exploring evolution on complex fitness landscapes 01.01.2011 Project funding (special)
106751 The evolutionary ecology of infectious pathogens 01.03.2005 SNSF Professorships

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