On differentiating selective and neutral evolutionary processes

摘要 世纪初，S. Wright和R.A. Fisher 发展了许多数学和概念框架的基础研究， 种群水平的过程决定了物种内和物种间观察到的变化。然而，在这方面， 正如几十年来发表的互动所证明的那样，他们对以下问题持有强烈不同的观点： 适应性与非适应性过程在推动进化中的相对重要性。指出的 Crow（2008）指出，这些问题并没有真正得到解决，而是“被抛弃了 更容易处理的研究“随着M. Kimura和T. Ohta提出了随机效应的相对贡献，并在此基础上提出了随机效应的相对贡献的概念.赖特，收到 重新注意。在随后的几十年里，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 基因漂移的作用然而，随后的研究涉及到联系，而不是直接的选择， 这些影响重新引发了先前的辩论。也就是说，无论是大类的强烈和 中性理论假设的弱有害变体，以及它们的相关关联 选择效应（即，背景选择），足以解释基因组范围的模式， 变异;或者是否有更主要的一类有益变异，以及它们的相关关联 选择效应（即，选择性扫描）。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立的空模型-也就是说，一个模型， 遗传漂变是由一个现实的人口历史，以及一个现实的分布， 适合度效应总结了直接和联系的净化选择的普遍效应。 如果没有这个零模型，结合这些进化过程， 发生时，根本不可能量化自适应的周期性频率。 这些过程还起到塑造多态性和分歧模式的作用。未来 工作将集中在必要的理论和统计发展，以应用于 在Wright-Fisher背景下，以小后代分布为特征的生物 模型和金曼聚结剂（例如，人类），以及大的后代分布在 Moran模型和多重合并（例如，病毒）。总的来说，产品 这一研究将是一个框架，推断进化适当的空模型 广泛适用于整个生命之树，这将使该领域能够直接解决这个长期存在的问题。 长期和根本性的辩论，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.