Waiting with and without recombination: The time to production of a double mutant
Waiting with and without recombination: The time to production of a double mutant
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DOI：
10.1006/tpbi.1997.1358
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发表时间：
1998-06-01
影响因子：
1.4
通讯作者：
Feldman, MW
中科院分区：
文献类型：
--
作者：
Christiansen, FB;Otto, SP;Feldman, MW
R. A. Fisher和H.穆勒在20世纪30年代提出，重组的一个主要进化优势是，它允许有利的突变在个体内组合，即使它们最初出现在不同的个体中。在双基因座、双等位基因模型中，通过计算直到新的基因型组合首次出现在单倍体群体中的平均等待时间来评估这种效应。三个近似的开发和比较，在有限的人口中的随机遗传漂变的Wright-Fisher过程的Monte Carlo模拟。首先，一种基于单突变体的确定性积累的粗略方法，在没有重组的情况下产生1/根N μ（2）的等待时间，在两个基因座之间重组的情况下产生1/（3）根1/3RN μ（2）的等待时间，其中μ是突变率，N是单倍体群体大小，R是重组率。其次，等待时间计算为从分支过程近似获得的非均匀几何分布的期望值。这给出了N mu大的精确估计。小值的N μ的估计值是相当低于模拟值。最后，Wright-Fisher过程的扩散分析提供了N μ small的精确估计，并且扩散过程的时间尺度显示了R = 0和R >> 0之间的差异，其数量级与确定性分析中所见的相同。在没有重组的情况下，通过使用高N μ的分支过程和低N μ的扩散近似，可以获得等待时间的准确近似值。对于低N μ，等待时间很好地近似为1/root 8 N（2）mu（3）。当R >> 0时，观察到以下对N mu的依赖性：对于N mu > 1，等待时间实际上与复合无关，并且可以用分支过程近似来描述。对于N亩近似为1的等待时间是很好地描述了一个简化的扩散近似，假设对称的单突变体的频率。对于N μ
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/root N mu(2) with no recombination and 1/ (3)root 1/3RN mu(2) with recombination between the two loci, where mu 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 N mu large. The estimates for small values of N mu are considerably lower than the simulated values. Finally, diffusion analysis of the Wright-Fisher process provides accurate estimates for N mu 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 N mu and the diffusion approximation for low N mu. For low N mu the waiting time is well approximated by 1/root 8N(2)mu(3). With R >> 0, the following dependence on N mu is observed: For N mu > 1 the waiting time is virtually independent of recombination and is well described by the branching process approximation. For N mu approximate to 1 the waiting time is well described by a simplified diffusion approximation that assumes symmetry in the frequencies of single mutants. For N mu