Department of Mathematics, Uppsala University, 752 37 Uppsala, Sweden.
Department of Ecology and Genetics, Uppsala University, 752 36 Uppsala, Sweden.
Genome Biol Evol. 2022 May 3;14(5). doi: 10.1093/gbe/evac058.
The nearly neutral theory is a common framework to describe natural selection at the molecular level. This theory emphasizes the importance of slightly deleterious mutations by recognizing their ability to segregate and eventually get fixed due to genetic drift in spite of the presence of purifying selection. As genetic drift is stronger in smaller than in larger populations, a correlation between population size and molecular measures of natural selection is expected within the nearly neutral theory. However, this hypothesis was originally formulated under equilibrium conditions. As most natural populations are not in equilibrium, testing the relationship empirically may lead to confounded outcomes. Demographic nonequilibria, for instance following a change in population size, are common scenarios that are expected to push the selection-drift relationship off equilibrium. By explicitly modeling the effects of a change in population size on allele frequency trajectories in the Poisson random field framework, we obtain analytical solutions of the nonstationary allele frequency spectrum. This enables us to derive exact results of measures of natural selection and effective population size in a demographic nonequilibrium. The study of their time-dependent relationship reveals a substantial deviation from the equilibrium selection-drift balance after a change in population size. Moreover, we show that the deviation is sensitive to the combination of different measures. These results therefore constitute relevant tools for empirical studies to choose suitable measures for investigating the selection-drift relationship in natural populations. Additionally, our new modeling approach extends existing population genetics theory and can serve as foundation for methodological developments.
近中性理论是描述分子水平自然选择的常用框架。该理论通过认识到轻微有害突变的能力，强调了其重要性，尽管存在净化选择，但这些突变能够通过遗传漂变分离并最终固定下来。由于遗传漂变在较小的种群中比在较大的种群中更强，因此在近中性理论中预计会存在种群大小与自然选择的分子度量之间的相关性。然而，该假设最初是在平衡条件下提出的。由于大多数自然种群都不在平衡状态，因此通过经验检验这种关系可能会导致混淆的结果。例如，人口规模发生变化后，人口非平衡的情况很常见，预计会使选择-漂变关系脱离平衡。通过在泊松随机场框架中明确建模种群大小变化对等位基因频率轨迹的影响，我们获得了非平稳等位基因频率谱的解析解。这使我们能够在人口非平衡状态下推导出自然选择和有效种群大小的度量的精确结果。研究它们的时变关系表明，在种群大小发生变化后，平衡选择-漂变平衡会发生实质性偏离。此外，我们表明，这种偏差对不同度量的组合很敏感。因此，这些结果构成了实证研究的相关工具，可用于选择合适的度量来研究自然种群中的选择-漂变关系。此外，我们的新建模方法扩展了现有的群体遗传学理论，并可为方法学的发展提供基础。
