Zeng Kai, Corcoran Pádraic
Department of Animal and Plant Sciences, University of Sheffield, Sheffield S10 2TN, United Kingdom
Department of Animal and Plant Sciences, University of Sheffield, Sheffield S10 2TN, United Kingdom.
Genetics. 2015 Dec;201(4):1539-54. doi: 10.1534/genetics.115.178558. Epub 2015 Oct 4.
It is well known that most new mutations that affect fitness exert deleterious effects and that natural populations are often composed of subpopulations (demes) connected by gene flow. To gain a better understanding of the joint effects of purifying selection and population structure, we focus on a scenario where an ancestral population splits into multiple demes and study neutral diversity patterns in regions linked to selected sites. In the background selection regime of strong selection, we first derive analytic equations for pairwise coalescent times and FST as a function of time after the ancestral population splits into two demes and then construct a flexible coalescent simulator that can generate samples under complex models such as those involving multiple demes or nonconservative migration. We have carried out extensive forward simulations to show that the new methods can accurately predict diversity patterns both in the nonequilibrium phase following the split of the ancestral population and in the equilibrium between mutation, migration, drift, and selection. In the interference selection regime of many tightly linked selected sites, forward simulations provide evidence that neutral diversity patterns obtained from both the nonequilibrium and equilibrium phases may be virtually indistinguishable for models that have identical variance in fitness, but are nonetheless different with respect to the number of selected sites and the strength of purifying selection. This equivalence in neutral diversity patterns suggests that data collected from subdivided populations may have limited power for differentiating among the selective pressures to which closely linked selected sites are subject.
众所周知,大多数影响适应性的新突变会产生有害影响,并且自然种群通常由通过基因流动连接的亚种群(deme)组成。为了更好地理解纯化选择和种群结构的联合效应,我们关注一种情况,即一个祖先种群分裂成多个deme,并研究与选择位点相关区域的中性多样性模式。在强选择的背景选择模式下,我们首先推导了成对合并时间和FST的解析方程,作为祖先种群分裂成两个deme后时间的函数,然后构建了一个灵活的合并模拟器,该模拟器可以在复杂模型下生成样本,例如涉及多个deme或非保守迁移的模型。我们进行了广泛的正向模拟,以表明新方法可以准确预测祖先种群分裂后的非平衡阶段以及突变、迁移、漂移和选择之间平衡状态下的多样性模式。在许多紧密连锁的选择位点的干扰选择模式下,正向模拟提供了证据,即对于适应性具有相同方差但在选择位点数量和纯化选择强度方面不同的模型,从非平衡阶段和平衡阶段获得的中性多样性模式实际上可能无法区分。中性多样性模式的这种等效性表明,从细分种群收集的数据在区分紧密连锁的选择位点所面临的选择压力方面可能具有有限的能力。