Dynamics of Contemporary Genomic Evolution in Replicate Threespine Stickleback Populations

我们传统上认为生物体对新环境的适应是从一个新的生物的出现开始的 有利的突变和传播到人群中。虽然这种观点很好地适用于微生物，如酵母或 细菌，通常需要更长的时间才能产生新的突变，并在大型、不那么丰富的 物种，当它们这样做的时候，它们更有可能迷失。因此，自然选择作用于新的 在人类进化的最后25万年里，突变显然是罕见的。另一种观点是 可能适用于人类的适应正在出现；许多突变在人群中持续很长一段时间 “持续遗传变异”(SGV)，即使它们对生存机会有微弱甚至不利的影响 并繁殖(即自然选择)。当环境发生变化或人员迁移时，SGV中的变体 可能会变得非常有利，使人们能够迅速适应新的环境。的确有 越来越多的证据表明，SGV对许多物种在短期内的适应至关重要，并且对 大多数复杂的人类特征(包括疾病特征)和人类病原体(如艾滋病毒)的抗药性。 然而，尽管基于SGV的人类适应的例子越来越多，但令人惊讶的是，人们对此知之甚少。 无论是理论上还是经验上，都是关于基于特殊群体的适应的​进化动力学​。在过去的五年中 多年来，三刺鱼(​Gasterost​eus aculeatus)已成为我国重要的养殖对象 基于SGV的适应性研究。海上刺鱼含有丰富的SGV，曾多次入侵 淡水。它们对淡水的适应大多发生在它们殖民淡水后的十年内，这取决于 在SGV上。事实上，同一基因的SGV显然有助于皮肤色素沉着的适应。 人类和TS的时间尺度相似(按世代计算)。这个项目的总体目标是了解 TS中基于SGV的适应进化动力学研究。实现这一目标的第一个目标是排序 来自阿拉斯加5个海上种群的约1,000只海洋TS的基因组鉴定SGV和 估计在祖先环境中淡水适应性SGV变种的相对丰度。这个 第二个目标是在10年内每年对附近三个阿拉斯加湖的TS样本进行排序，包括 紧接着这些湖泊就被海上运行的TS殖民了。这将使我们能够直接观察SGV 在适应的最早阶段相对丰度的变化，当时大多数从海上运行进化到 淡水特征会发生。第三个目标是对同时出生一组TS(即，队列)进行排序 在两个新的湖泊种群中，通过两年的生命周期每两周到每月一次的间隔，允许识别 在适应的生命周期中，哪些原始SGV变体为特定事件赋予了优势 淡水TS。这项研究将为基于SGV的适应动力学提供独特的见解 对于更好地了解人类及其病原体如何在短时间内适应新环境至关重要 比例。

We traditionally envision adaptation of organisms to new environments as starting with appearance of a new favorable mutation and spreading to the population. While this view applies well to microbes, such as yeast or bacteria, it usually takes much longer for new mutations to arise and spread in large-bodied, less-abundant species, and when they do, they are more likely to be lost. Accordingly, natural selection acting on new mutations apparently was rare during the last 250,000 years of human evolution. An alternative view for adaptation that may apply well to humans is emerging; many mutations persist in populations for a long time as “standing genetic variation” (SGV) even though they have weak or even adverse effects on chances to survive and reproduce (i.e., natural selection). When an environment changes or people migrate, variants in the SGV may become highly advantageous, allowing the population to adapt quickly to its new surroundings. There is growing evidence that SGV is crucial for adaptation of many species over short time scales, and is crucial for most complex human traits (including those for disease) and drug resistance in human pathogens (e.g., HIV). However, while examples of adaptation based on SGV in humans are growing, surprisingly little is known, either theoretically or empirically, about the ​evolutionary dynamics​ of adaptation based on SGV. In the last five years, the Threespine Stickleback (TS, ​Gasterost​eus aculeatus) fish has emerged as the premier subject to study adaptation based on SGV. Sea-run stickleback contain abundant SGV and have repeatedly invaded fresh water. Much of their adaptation to fresh water occurs within a decade after they colonize it and depends on SGV. Indeed, SGV for the very same gene has apparently contributed to adaptation for skin pigmentation in both humans and TS on similar time scales (in generations). The overall goal of this project is to understand the evolutionary dynamics of adaptation based on SGV in TS. The first aim to reach this goal is to sequence the genomes of ~1,000 marine TS from five Alaskan sea-run populations to identify genes with SGV and estimate the relative abundance of freshwater-adaptive SGV variants in the ancestral environment. The second aim is to sequence TS samples from three nearby Alaskan lakes annually for 10 years, including immediately after these lakes were colonized by sea-run TS. This will enable direct observation of how SGV changes in relative abundance during the earliest stages of adaptation, when most evolution from a sea-run to freshwater traits occurs. The third aim is to sequence a group of TS born simultaneously (i.e., a cohort) at biweekly to monthly intervals through the two-year life cycle in two new lake populations, allowing identification of which original SGV variants confer advantages for specific events during the life-cycle of adapting freshwater TS. This study will provide unique insights into the dynamics of adaptation based on SGV, which will be vital to better understand how humans and their pathogens adapt to new environments over short time scales.