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Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18135-40. Epub 2007 Nov 5.

Clonal interference in large populations.

Author information

  • 1Institut für Theoretische Physik, Universität zu Köln, Zülpicher Strasse 77, 50937 Köln, Germany.

Abstract

Clonal interference, the competition between lineages arising from different beneficial mutations in an asexually reproducing population, is an important factor determining the tempo and mode of microbial adaptation. The standard theory of this phenomenon neglects the occurrence of multiple mutations as well as the correlation between loss by genetic drift and clonal competition, which is questionable in large populations. Working within the Wright-Fisher model with multiplicative fitness (no epistasis), we determine the rate of adaptation asymptotically for very large population sizes and show that the standard theory fails in this regime. Our study also explains the success of the standard theory in predicting the rate of adaptation for moderately large populations. Furthermore, we show that the nature of the substitution process changes qualitatively when multiple mutations are allowed for, because several mutations can be fixed in a single fixation event. As a consequence, the index of dispersion for counts of the fixation process displays a minimum as a function of population size, whereas the origination process of fixed mutations becomes completely regular for very large populations. We find that the number of mutations fixed in a single event is geometrically distributed as in the neutral case. These conclusions are based on extensive simulations combined with analytic results for the limit of infinite population size.

PMID:
17984061
[PubMed - indexed for MEDLINE]
PMCID:
PMC2084309
Free PMC Article

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