Originally published as Genetics Published Articles Ahead of Print on May 4, 2007.

Genetics, Vol. 176, 1759-1798, July 2007, Copyright © 2007
doi:10.1534/genetics.106.067678

Beneficial Mutation–Selection Balance and the Effect of Linkage on Positive Selection

* Department of Physics, {dagger} Department of Molecular and Cell Biology and {ddagger} Division of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138

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

When beneficial mutations are rare, they accumulate by a series of selective sweeps. But when they are common, many beneficial mutations will occur before any can fix, so there will be many different mutant lineages in the population concurrently. In an asexual population, these different mutant lineages interfere and not all can fix simultaneously. In addition, further beneficial mutations can accumulate in mutant lineages while these are still a minority of the population. In this article, we analyze the dynamics of such multiple mutations and the interplay between multiple mutations and interference between clones. These result in substantial variation in fitness accumulating within a single asexual population. The amount of variation is determined by a balance between selection, which destroys variation, and beneficial mutations, which create more. The behavior depends in a subtle way on the population parameters: the population size, the beneficial mutation rate, and the distribution of the fitness increments of the potential beneficial mutations. The mutation–selection balance leads to a continually evolving population with a steady-state fitness variation. This variation increases logarithmically with both population size and mutation rate and sets the rate at which the population accumulates beneficial mutations, which thus also grows only logarithmically with population size and mutation rate. These results imply that mutator phenotypes are less effective in larger asexual populations. They also have consequences for the advantages (or disadvantages) of sex via the Fisher–Muller effect; these are discussed briefly.


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