Melfi Andrew, Viswanath Divakar
Department of Mathematics, University of Michigan, United States.
Theor Popul Biol. 2018 May;121:60-71. doi: 10.1016/j.tpb.2018.04.001. Epub 2018 Apr 12.
The Kingman coalescent is a commonly used model in genetics, which is often justified with reference to the Wright-Fisher (WF) model. Current proofs of convergence of WF and other models to the Kingman coalescent assume a constant sample size. However, sample sizes have become quite large in human genetics. Therefore, we develop a convergence theory that allows the sample size to increase with population size. If the haploid population size is N and the sample size is N, ϵ>0, we prove that Wright-Fisher genealogies involve at most a single binary merger in each generation with probability converging to 1 in the limit of large N. Single binary merger or no merger in each generation of the genealogy implies that the Kingman partition distribution is obtained exactly. If the sample size is N, Wright-Fisher genealogies may involve simultaneous binary mergers in a single generation but do not involve triple mergers in the large N limit. The asymptotic theory is verified using numerical calculations. Variable population sizes are handled algorithmically. It is found that even distant bottlenecks can increase the probability of triple mergers as well as simultaneous binary mergers in WF genealogies.
金曼合并模型是遗传学中常用的模型,通常借助赖特-费希尔(WF)模型来证明其合理性。目前关于WF模型及其他模型向金曼合并模型收敛的证明都假定样本大小恒定。然而,在人类遗传学中样本大小已经变得相当大。因此,我们发展了一种收敛理论,该理论允许样本大小随种群大小增加。如果单倍体种群大小为N,样本大小为n,ε>0,我们证明在大N极限情况下,赖特-费希尔系谱在每一代中最多涉及一次二元合并的概率收敛到1。系谱的每一代中出现一次二元合并或不出现合并意味着恰好得到金曼划分分布。如果样本大小为n,赖特-费希尔系谱在单代中可能涉及同时发生的二元合并,但在大N极限情况下不涉及三元合并。通过数值计算验证了渐近理论。可变种群大小通过算法处理。研究发现,即使是遥远的瓶颈效应也会增加WF系谱中三元合并以及同时发生的二元合并的概率。