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

Michael M. Desai^*,,1 and Daniel S. Fisher^*,,2

^* Department of Physics, Department of Molecular and Cell Biology and 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.

Related articles in Genetics:

ISSUE HIGHLIGHTS

Genetics 2007 176: NP. [Full Text]  

This article has been cited by other articles:

				B. S. Khatri, T. C. B. McLeish, and R. P. Sear Statistical mechanics of convergent evolution in spatial patterning PNAS, June 16, 2009; 106(24): 9564 - 9569. [Abstract] [Full Text] [PDF]

				R. A. Neher and B. I. Shraiman Competition between recombination and epistasis can cause a transition from allele to genotype selection PNAS, April 21, 2009; 106(16): 6866 - 6871. [Abstract] [Full Text] [PDF]

				R. C. Woodruff and M. Zhang Adaptation from Leaps in the Dark J. Hered., January 1, 2009; 100(1): 7 - 10. [Abstract] [Full Text] [PDF]

				C. A. Fogle, J. L. Nagle, and M. M. Desai Clonal Interference, Multiple Mutations and Adaptation in Large Asexual Populations Genetics, December 1, 2008; 180(4): 2163 - 2173. [Abstract] [Full Text] [PDF]

				M. M. Desai and J. B. Plotkin The Polymorphism Frequency Spectrum of Finitely Many Sites Under Selection Genetics, December 1, 2008; 180(4): 2175 - 2191. [Abstract] [Full Text] [PDF]

				Z Patwa and L.M Wahl The fixation probability of beneficial mutations J R Soc Interface, November 6, 2008; 5(28): 1279 - 1289. [Abstract] [Full Text] [PDF]

				L.-M. Chevin and F. Hospital Selective Sweep at a Quantitative Trait Locus in the Presence of Background Genetic Variation Genetics, November 1, 2008; 180(3): 1645 - 1660. [Abstract] [Full Text] [PDF]

				E. Brunet, I. M. Rouzine, and C. O. Wilke The Stochastic Edge in Adaptive Evolution Genetics, May 1, 2008; 179(1): 603 - 620. [Abstract] [Full Text] [PDF]

International Access Link

Online ISSN: 1943-2361  Print ISSN: 0016-6731
Copyright 2009 by the Genetics Society of America
phone: 412-268-1812   fax: 412-268-1813   email: genetics-gsa{at}andrew.cmu.edu