Experimental studies on ecological and genetic complexity in adaptation

为什么自然世界如此多样化？可以说，这个问题仍然是生物学中未解决的核心问题之一。我的研究旨在提供答案。我的目标是为生物多样性的起源和命运提供一个普遍的、以经验为基础的理论。我使用微生物模型系统通过实验来测试进化的基础理论，这种技术称为实验进化。这种方法使我能够实时跟踪多样性的出现和命运，并与基因组测序相结合，使我能够识别负责适应和多样化的遗传变化。这里提出的研究询问，当面对比之前考虑的更复杂的生态和遗传系统时，我们现有的模型在解释适应性多样化模式方面表现如何。 我们的短期目标是（1）评估网络拓扑对集合种群适应的影响，（2）测试适应度景观结构（基因型到适应度的映射）在适应过程中如何变化的预测。更具体地说，我们要问的是，空间结构（通过分散连接的亚种群网络）是否会影响均匀环境中的选择结果。如果环境在空间上也是可变的，即不同的斑块包含不同的资源或压力，这种情况应该促进多样性的进化，该怎么办？适应模型在预测哪些基因变化序列会导致适应方面有多好？ 这项工作是由基础问题推动的，因此将有助于增进进化、遗传学和生态学方面的基础知识，并在这笔赠款的过程中培训至少 17 名从本科生到博士的高素质人才。然而，大部分研究都是通过病原微生物的管理来进行的，特别是在抗菌素耐药性方面。人们很早就认识到，我们在治疗传染病方面面临的许多挑战的核心都是进化。这项工作是评估进化理论的第一步，该理论可以为与传染病治疗和管理相关的实际解决方案提供信息。

Why is the natural world so diverse? Arguably, this question remains one of the central unresolved problems in biology. My research aims to supply an answer. My aim is to provide a general, empirically-grounded theory for the origins and fate of biodiversity. I use microbial model systems to test foundational theories in evolution through experiment to do this, a technique known as experimental evolution. This approach allows me to track the emergence and fate of diversity in real time and, in combination with genome sequencing, allows me to identify the genetic changes responsible for adaptation and diversification. The research proposed here asks how well our existing models fare at explaining patterns of adaptive diversification when confronted with more ecologically and genetically complex systems than have been considered previously. Our short-term objectives are (1) to evaluate the impact of network topology on adaptation in metapopulations and, (2) test predictions on how the structure of fitness landscapes - the mapping of genotype to fitness - changes during adaptation. More specifically, we ask whether spatial structure, the network of sub-populations connected by dispersal, impacts the outcome of selection in an otherwise uniform environment. What if the environment is also spatially variable, in the sense that different patches contain different resources or stresses, a situation that should promote the evolution of diversity? How good are models of adaptation at predicting which sequence of genetic changes cause adaptation? This work is motivated by foundational problems, and so will contribute to basic knowledge in evolution, genetics, and ecology and training at least 17 highly qualified people, from undergraduate through to PhD, over the course of this grant. However, the lens through which much of this research happens is the management of pathogenic microbes, especially in regards to antimicrobial resistance. It has long been appreciated that many of the challenges we face in treating infectious disease have evolution at their core. This work constitutes a first step towards evaluating evolutionary theories that can inform practical solutions associated with the treatment and management of infectious disease.