Recombination, Genetic Interactions, and Observable Evolutionary Dynamics

该项目的目标是通过分析建立在各种关键特征中的各种模型，对具有丰富选择和重组的大型种群的进化动力学进行定量理解。在几种情况下，将研究在一个谱系中积累的多个有益突变与分离并将这些突变集合在一起的重组之间的相互作用：重组，个体之间的染色体交换，而不像流感病毒那样发生重组;基因组的小片段转移，如细菌之间的横向基因转移;在无性进化的群体之间偶尔的交配，如在酵母中;以及由染色体的线性结构引起的连锁程度的各种近似。突变之间的上位性相互作用以及不断变化的连锁导致个体基因选择和基因组选择之间的平衡：这将被探索为各种模型的相互作用，重点是罕见的统计特性，占主导地位的未来进化突变的良好组合。上位性模型将由合作者进行的芽殖酵母实验室进化实验提供信息。在无性进化的种群内部或之间进行交配，这些种群已经被“条形码”，应该提供关于父母及其后代健康的关键信息，而所开发的理论将能够预测性行为的益处，这些益处可以在未来的实验中进行测试。除了所有个体直接竞争的混合良好的种群之外，还将研究在实验室中可以实现的其他形式的竞争（例如选择种群中最好的一半）。还将研究空间结构以及当地竞争和混合在较长时间尺度上的相互作用，重点是重组对进化速度和多样性动态的影响。 与几个用酵母或细菌进行实验室进化实验的小组的合作将进一步发展，以获得建模所需的统计信息，并提出和计划未来的实验。将与合作者一起对细菌种群的深度测序数据进行分析，以推断进化历史的各个方面，包括重组，并为未来最具信息性的采样和测序制定计划。参与的学生和博士后将大大受益于来自不同领域的几个教师的指导。除了研究，PI正在为定量科学家和生物学家开发新的进化课程：课堂讲稿将在互联网上提供。PI还将进一步参与教育公众关于进化的知识，包括未来的挑战，以及进化理论的成功。

The goal of this project is to develop quantitative understanding of the evolutionary dynamics of large populations with abundant selection and recombination by analyzing a variety of models that build in various of the key features. The interplay between multiple beneficial mutations accumulating in one lineage and recombination that breaks apart and brings together collections of such mutations will be studied in several situations: re-assortment, the exchange of chromosomes between individuals without recombination as occurs for influenza viruses; transfer of small segments of a genome as in lateral gene transfer between bacteria; occasional mating between otherwise asexually evolving populations, as in yeast; and various approximations of the spectrum of degrees of linkage that arise from the linear structure of chromosomes. Epistatic interactions between mutations together with changing linkage leads to a balance between selection on individual genes and selection on genomes: this will be explored for various models of the interactions focusing on the statistical properties of the rare, anomalously good combinations of mutations that dominate the future evolution. The models of epistasis will be informed by, and inform, experiments on laboratory evolution of budding yeast carried out by collaborators. Mating within or between asexually evolved populations that have been "barcoded", should provide crucial information about the fitness of parents and their offspring, and the theory developed will enable predictions about the benefits of sex that can be tested in future experiments. Going beyond well-mixed populations in which all individuals compete directly, other forms of competition that could be realized in the laboratory (such as selection of the best half of a population) will be studied. Spatial structure and the interplay between local competition and mixing on longer time scales will also be investigated, focusing on the effects of recombination on rates of evolution and dynamics of diversity. Collaborations with several groups carrying out laboratory evolution experiments with yeast or bacteria will be further developed to obtain statistical information needed for the modeling, and to propose and plan future experiments. Analysis of deep sequencing data of bacterial populations will be carried out with collaborators to infer aspects of the evolutionary history, including recombination, and to develop plans for the most informative future sampling and sequencing. The students and postdocs involved will greatly benefit from mentoring by several faculty from different fields. Beyond the research, the PI is developing new courses on evolution for quantitative scientists and biologists: lecture notes will be made available on the internet. The PI will also become further involved in educating the general public about evolution, including the future challenges, as well as the successes, of evolutionary theory.