### Abstract

R. A. Fisher and H. J. Muller argued in the 1930s that a major evolutionary advantage of recombination is that it allows favorable mutations to be combined within an individual even when they first appear in different individuals. This effect is evaluated in a two-locus, two-allele model by calculating the average waiting time until a new genotypic combination first appears in a haploid population. Three approximations are developed and compared with Monte Carlo simulations of the Wright-Fisher process of random genetic drift in a finite population. First, a crude method, based on the deterministic accumulation of single mutants, produces a waiting time of 1/√Nμ^{2} with no recombination and 1/3√1/3 RNμ^{2} with recombination between the two loci, where μ is the mutation rate, N is the haploid population size, and R is the recombination rate. Second, the waiting time is calculated as the expected value of a heterogeneous geometric distribution obtained from a branching process approximation. This gives accurate estimates for Nμ large. The estimates for small values of Nμ are considerably lower than the simulated values. Finally, diffusion analysis of the Wright-Fisher process provides accurate estimates for Nμ small, and the time scales of the diffusion process show a difference between R = 0 and for R >> 0 of the same order of magnitude as seen in the deterministic analysis. In the absence of recombination, accurate approximations to the waiting time are obtained by using the branching process for high Nμ and the diffusion approximation for low Nμ. For low Nμ the waiting time is well approximated by 1/√8N^{2}μ^{3}. With R >> 0, the following dependence on Nμ is observed: For Nμ > 1 the waiting time is virtually independent of recombination and is well described by the branching process approximation. For Nμ ≃ 1 the waiting time is well described by a simplified diffusion approximation that assumes symmetry in the frequencies of single mutants. For Nμ << 1 the waiting time is well described by the diffusion approximation allowing asymmetry in the frequencies of single mutants. Recombination lowers the waiting time until a new genotypic combination first appears, but the effect is small compared to that of the mutation rate and population size. For large Nμ, recombination has a negligible effect, and its effect is strongest for small Nμ, in which case the waiting time approaches a fixed fraction of the waiting time for R = 0. Free combination lowers the waiting time to about 45% of the waiting time for absolute linkage for small Nμ. Selection has little effect on the importance of recombination in general.

Original language | English (US) |
---|---|

Pages (from-to) | 199-215 |

Number of pages | 17 |

Journal | Theoretical Population Biology |

Volume | 53 |

Issue number | 3 |

DOIs | |

State | Published - Jun 1998 |

Externally published | Yes |

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### ASJC Scopus subject areas

- Agricultural and Biological Sciences(all)
- Ecology, Evolution, Behavior and Systematics

### Cite this

*Theoretical Population Biology*,

*53*(3), 199-215. https://doi.org/10.1006/tpbi.1997.1358

**Waiting with and without recombination : The time to production of a double mutant.** / Christiansen, Freddy B.; Otto, Sarah P.; Bergman, Aviv; Feldman, Marcus W.

Research output: Contribution to journal › Article

*Theoretical Population Biology*, vol. 53, no. 3, pp. 199-215. https://doi.org/10.1006/tpbi.1997.1358

}

TY - JOUR

T1 - Waiting with and without recombination

T2 - The time to production of a double mutant

AU - Christiansen, Freddy B.

AU - Otto, Sarah P.

AU - Bergman, Aviv

AU - Feldman, Marcus W.

PY - 1998/6

Y1 - 1998/6

N2 - R. A. Fisher and H. J. Muller argued in the 1930s that a major evolutionary advantage of recombination is that it allows favorable mutations to be combined within an individual even when they first appear in different individuals. This effect is evaluated in a two-locus, two-allele model by calculating the average waiting time until a new genotypic combination first appears in a haploid population. Three approximations are developed and compared with Monte Carlo simulations of the Wright-Fisher process of random genetic drift in a finite population. First, a crude method, based on the deterministic accumulation of single mutants, produces a waiting time of 1/√Nμ2 with no recombination and 1/3√1/3 RNμ2 with recombination between the two loci, where μ is the mutation rate, N is the haploid population size, and R is the recombination rate. Second, the waiting time is calculated as the expected value of a heterogeneous geometric distribution obtained from a branching process approximation. This gives accurate estimates for Nμ large. The estimates for small values of Nμ are considerably lower than the simulated values. Finally, diffusion analysis of the Wright-Fisher process provides accurate estimates for Nμ small, and the time scales of the diffusion process show a difference between R = 0 and for R >> 0 of the same order of magnitude as seen in the deterministic analysis. In the absence of recombination, accurate approximations to the waiting time are obtained by using the branching process for high Nμ and the diffusion approximation for low Nμ. For low Nμ the waiting time is well approximated by 1/√8N2μ3. With R >> 0, the following dependence on Nμ is observed: For Nμ > 1 the waiting time is virtually independent of recombination and is well described by the branching process approximation. For Nμ ≃ 1 the waiting time is well described by a simplified diffusion approximation that assumes symmetry in the frequencies of single mutants. For Nμ << 1 the waiting time is well described by the diffusion approximation allowing asymmetry in the frequencies of single mutants. Recombination lowers the waiting time until a new genotypic combination first appears, but the effect is small compared to that of the mutation rate and population size. For large Nμ, recombination has a negligible effect, and its effect is strongest for small Nμ, in which case the waiting time approaches a fixed fraction of the waiting time for R = 0. Free combination lowers the waiting time to about 45% of the waiting time for absolute linkage for small Nμ. Selection has little effect on the importance of recombination in general.

AB - R. A. Fisher and H. J. Muller argued in the 1930s that a major evolutionary advantage of recombination is that it allows favorable mutations to be combined within an individual even when they first appear in different individuals. This effect is evaluated in a two-locus, two-allele model by calculating the average waiting time until a new genotypic combination first appears in a haploid population. Three approximations are developed and compared with Monte Carlo simulations of the Wright-Fisher process of random genetic drift in a finite population. First, a crude method, based on the deterministic accumulation of single mutants, produces a waiting time of 1/√Nμ2 with no recombination and 1/3√1/3 RNμ2 with recombination between the two loci, where μ is the mutation rate, N is the haploid population size, and R is the recombination rate. Second, the waiting time is calculated as the expected value of a heterogeneous geometric distribution obtained from a branching process approximation. This gives accurate estimates for Nμ large. The estimates for small values of Nμ are considerably lower than the simulated values. Finally, diffusion analysis of the Wright-Fisher process provides accurate estimates for Nμ small, and the time scales of the diffusion process show a difference between R = 0 and for R >> 0 of the same order of magnitude as seen in the deterministic analysis. In the absence of recombination, accurate approximations to the waiting time are obtained by using the branching process for high Nμ and the diffusion approximation for low Nμ. For low Nμ the waiting time is well approximated by 1/√8N2μ3. With R >> 0, the following dependence on Nμ is observed: For Nμ > 1 the waiting time is virtually independent of recombination and is well described by the branching process approximation. For Nμ ≃ 1 the waiting time is well described by a simplified diffusion approximation that assumes symmetry in the frequencies of single mutants. For Nμ << 1 the waiting time is well described by the diffusion approximation allowing asymmetry in the frequencies of single mutants. Recombination lowers the waiting time until a new genotypic combination first appears, but the effect is small compared to that of the mutation rate and population size. For large Nμ, recombination has a negligible effect, and its effect is strongest for small Nμ, in which case the waiting time approaches a fixed fraction of the waiting time for R = 0. Free combination lowers the waiting time to about 45% of the waiting time for absolute linkage for small Nμ. Selection has little effect on the importance of recombination in general.

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UR - http://www.scopus.com/inward/citedby.url?scp=0032100195&partnerID=8YFLogxK

U2 - 10.1006/tpbi.1997.1358

DO - 10.1006/tpbi.1997.1358

M3 - Article

C2 - 9679320

AN - SCOPUS:0032100195

VL - 53

SP - 199

EP - 215

JO - Theoretical Population Biology

JF - Theoretical Population Biology

SN - 0040-5809

IS - 3

ER -