On differentiating selective and neutral evolutionary processes

摘要 在20世纪初创立种群遗传学时，S.Wright和R.A.Fisher 开发了许多数学和概念框架，这些框架是研究 种群水平的过程决定了观察到的物种内和物种间的差异。然而， 数十年的出版互动证明，他们对以下问题持有强烈不同的看法 适应性过程与非适应性过程在推动进化中的相对重要性。如上所述 J·克罗(2008)指出，这些问题并没有真正得到解决，而是被抛弃了 更倾向于更易处理的研究。 Ohta，随机效应的相对贡献，如S·赖特早先所主张的，收到了 重新引起人们的关注。在接下来的几十年里，进一步的理论发展以及 大规模测序数据的可用性确实压倒性地证明了重要的 基因漂移的作用。然而，随后的研究与联系选择有关，而不是直接选择 这些影响重新点燃了之前的辩论。也就是说，大阶级的强势和 中性理论下的弱有害变种及其相关联系 选择效应(即背景选择)足以解释全基因组模式 变异；或者是否有更主要的一类有益的变异及其相关联系 选择效果(即选择性扫描)是必需的。回答这个问题的主要困难是 问题源于我们缺乏一个适当的中性零模型--即，一个包含 由现实的人口历史和现实的人口分布所调节的遗传漂移 适应度效应总结了直接净化选择和关联净化选择的普遍影响。 如果没有包含这些进化过程的零模型，这些进化过程肯定是 发生时，量化自适应的周期频率是根本不可行的 此外，过程还在塑造多态和分歧的模式。未来 工作重点将放在必要的理论和统计发展上，以便应用于 在莱特-费舍尔的背景下以小子代分布为特征的有机体 模型和Kingman聚合体(例如人类)，以及大的后代在 Moran模型和多合并合并的背景(例如，病毒)。总体而言，该产品 这项研究将是一个框架，用于推断进化上合适的零模型 广泛适用于整个生命之树，这将使该领域能够直接解决这一长期- 长期和根本的辩论，并准确地确定适应的基因组目标。

ABSTRACT At the founding of population genetics in the early 20th century, S. Wright and R.A. Fisher developed much of the mathematical and conceptual framework underlying the study of population-level processes dictating variation observed within- and between-species. However, as evidenced by decades of published interactions, they held strongly differing views regarding the relative importance of adaptive vs. non-adaptive processes in driving evolution. As pointed out by J. Crow (2008), these issues were not really resolved, but "rather they were abandoned in favor of more tractable studies." With the proposal of the Neutral Theory by M. Kimura and T. Ohta, the relative contribution of stochastic effects, as earlier advocated by S. Wright, received renewed attention. In the following decades, further theoretical development as well as the availability of large-scale sequencing data have indeed overwhelmingly justified the important role of genetic drift. However, subsequent research related to linked, rather than direct, selection effects have re-ignited previous debates. Namely, whether the large class of strongly and weakly deleterious variants hypothesized under the Neutral Theory, and their related linked selection effects (i.e., background selection), are sufficient to explain genome wide patterns of variation; or whether a more predominant class of beneficial variants, and their related linked selection effects (i.e., selective sweeps), are required. The primary difficulty in answering this question stems from our lack of an appropriate neutral null model - that is, a model incorporating genetic drift as modulated by a realistic demographic history, as well as a realistic distribution of fitness effects summarizing the pervasive effects of both direct and linked purifying selection. Without this null model incorporating these evolutionary processes that are certain to be occurring, it is simply not feasible to quantify the periodic frequency with which adaptive processes are additionally acting to shape patterns of polymorphism and divergence. Future work will focus on the necessary theoretical and statistical developments for application to organisms characterized by small progeny distributions within the context of the Wright-Fisher model and Kingman coalescent (e.g., humans), as well as large progeny distributions within the context of the Moran model and multiple-merger coalescent (e.g., viruses). In total, the product of this research will be a framework for inferring evolutionarily appropriate null models applicable widely across the tree of life, that will enable the field to directly address this long- standing and fundamental debate, and to accurately identify genomic targets of adaptation.