DISSERTATION RESEARCH: Evolutionary Dynamics in Rapidly Evolving Populations

进化是生物学中最基本的过程之一，但众所周知，直接观察它是非常困难的。由于种群中不同基因变体之间的无情竞争，进化变化经过数千代的积累。除了少数罕见的情况，这种竞争的中间步骤在化石记录或现代物种的多样性中只被部分地保存下来。这使得很难获得建立和测试适应过程理论所需的经验数据。目前的工作旨在通过构建一个高分辨率的“分子化石记录”来填补这一空白，该记录记录了实验细菌种群的6万代进化。这个实验的独特持续时间——几乎是人类-黑猩猩分裂以来的四分之一的时间——允许人们直接观察分子进化的节奏在漫长的进化时间尺度上是如何变化的，当进化磁带重放时，生物复制将显示这一过程的哪些方面发生了变化。这些数据将在测试现有的适应恒定环境的理论方面发挥关键作用，并将有助于提出新的方法来模拟大型微生物种群的进化。为了实现这些目标，本研究将利用新的实验技术进行大规模多路DNA测序，以测量大肠杆菌进化实验中冷冻“化石记录”中的遗传多样性。结合新的生物信息学技术，这些定期保存的全种群样本允许人们追踪新突变的轨迹，因为它们出现并在种群中竞争主导地位。的吗?分子化石记录？从这一分析中得出的结论将构成对任何自然或实验群体中分子进化动力学的最长和最详细的看法。它们还将产生丰富的基因数据，用于比较不同人群和不同时间的分子趋同和平行模式。这些新的测量将与最近开发的计算框架相结合，以测试关于恒定环境中进化动力学的长期理论预测。

Evolution is one of the most fundamental processes in biology, but it can be notoriously difficult to observe directly. Evolutionary change accumulates over many thousands of generations as a result of a relentless competition between different genetic variants in a population. Except in a few rare cases, the intermediate steps of this competition are only partially preserved in the fossil record or the diversity of present-day species. This makes it hard to obtain the empirical data necessary for building and testing theories about the adaptive process. The present work aims to fill this void by constructing a high-resolution 'molecular fossil record' documenting 60,000 generations of evolution in experimental populations of bacteria. The unique duration of this experiment --- almost a quarter of the time since the human-chimpanzee split --- allows one to directly observe how the tempo of molecular evolution changes over long evolutionary timescales, and the biological replication will show which aspects of this process change when the evolutionary tape is replayed. These data will play a key role in testing existing theories of adaptation in a constant environment, and will help suggest new ways to model the evolution of large microbial populations. To achieve these goals, this study will leverage new experimental techniques for massively multiplexed DNA sequencing to measure genetic diversity in the frozen ``fossil record'' of a well-studied evolution experiment in Escherichia coli. Combined with new bioinformatic techniques, these regularly preserved, whole-population samples allow one to trace the trajectories of new mutations as they arise and compete for dominance in the population. The ?molecular fossil records? that emerge from this analysis will constitute the longest and most detailed view of the dynamics of molecular evolution in any natural or experimental population. They will also generate a wealth of genetic data that will be used to compare patterns of molecular convergence and parallelism across populations and through time. These new measurements will be combined with a recently developed computational framework in order to test long-standing theoretical predictions about the dynamics of evolution in a constant environment.