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MBE Advance Access published online on November 30, 2006
Molecular Biology and Evolution, doi:10.1093/molbev/msl189
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© The Author 2006. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted November 21, 2006

Research Article

Increasing Sequence Correlation Limits the Efficiency of Recombination in a Multi-Site Evolution Model

S. Gheorghiu-Svirschevski 1, I. M. Rouzine 1 *, and J.M. Coffin 1

1 Department of Microbiology and Molecular Biology Tufts University, Boston, MA 02111

* To whom correspondence should be addressed.
I. M. Rouzine, E-mail: irouzine{at}tufts.edu


  Abstract

The accumulation of pre-existing beneficial alleles in a haploid population, under selection and infrequent recombination, and in the absence of new mutation events, is studied numerically by means of detailed Monte Carlo simulations. On the one hand, we confirm our previous work, in that the accumulation rate follows modified single-site kinetics, with a time scale set by an effective selection coefficient s eff as shown in a previous work, and we confirm the qualitative features of the dependence of s eff on the population size and the recombination rate reported therein. In particular, we confirm the existence of a threshold population size below which evolution stops before the emergence of best-fit individuals. On the other hand, our simulations reveal that the population dynamics is essentially shaped by the steady accumulation of pairwise sequence correlation, causing sequence congruence in excess of what one would expect from a uniformly random distribution of alleles. By sequence congruence we understand here the opposite of genetic distance, that is, the fraction of monomorphic sites of specified allele type in a pair of genomes (individual sequences). The effective selection coefficient changes more rapidly with the recombination rate and has a higher threshold in this parameter than found in the previous work, which neglected correlation effects. We examine this phenomenon by monitoring the time dependence of sequence correlation based on a set of sequence congruence measures, and verify that it is not associated with the development of linkage disequilibrium. We also discuss applications to HIV evolution in infected individuals and potential implications for drug therapy.

Keywords: recombination; selection; model; numerical; simulation; correlation.
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