Originally published as Genetics Published Articles Ahead of Print on October 1, 2008.

Genetics, Vol. 180, 2163-2173, December 2008, Copyright © 2008
doi:10.1534/genetics.108.090019

Clonal Interference, Multiple Mutations and Adaptation in Large Asexual Populations

Craig A. Fogle^*, James L. Nagle^* and Michael M. Desai^,1

^* Department of Physics, University of Colorado, Boulder, Colorado 80309 and Lewis–Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544

¹ Corresponding author: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544.
E-mail: mmdesai{at}princeton.edu

Two important problems affect the ability of asexual populations to accumulate beneficial mutations and hence to adapt. First, clonal interference causes some beneficial mutations to be outcompeted by more-fit mutations that occur in the same genetic background. Second, multiple mutations occur in some individuals, so even mutations of large effect can be outcompeted unless they occur in a good genetic background that contains other beneficial mutations. In this article, we use a Monte Carlo simulation to study how these two factors influence the adaptation of asexual populations. We find that the results depend qualitatively on the shape of the distribution of the fitness effects of possible beneficial mutations. When this distribution falls off slower than exponentially, clonal interference alone reasonably describes which mutations dominate the adaptation, although it gives a misleading picture of the evolutionary dynamics. When the distribution falls off faster than exponentially, an analysis based on multiple mutations is more appropriate. Using our simulations, we are able to explore the limits of validity of both of these approaches, and we explore the complex dynamics in the regimes where neither one is fully applicable.

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