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Increasing sequence correlation limits the efficiency of recombination in a multisite evolution model.

TitleIncreasing sequence correlation limits the efficiency of recombination in a multisite evolution model.
Publication TypeJournal Article
Year of Publication2007
AuthorsGheorghiu-Svirschevski, S, IM Rouzine, Coffin, JM
JournalMol Biol Evol
Volume24
Issue2
Pagination574-86
Date Published2007 Feb
ISSN0737-4038
KeywordsAlleles, Drug Resistance, Viral, Evolution, Molecular, HIV, Humans, Kinetics, Linkage Disequilibrium, Models, Genetic, Monte Carlo Method, Recombination, Genetic
Abstract

The accumulation of preexisting 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 timescale 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.

DOI10.1093/molbev/msl189
Alternate JournalMol. Biol. Evol.
PubMed ID17138627
Grant ListK25 AI 01811 / AI / NIAID NIH HHS / United States
R01 CA 089441 / CA / NCI NIH HHS / United States
T32 AI007389 / AI / NIAID NIH HHS / United States