Experimental studies on ecological and genetic complexity in adaptation

为什么自然界如此多样化？可以说，这个问题仍然是生物学中悬而未决的核心问题之一。我的研究旨在提供一个答案。我的目的是为生物多样性的起源和命运提供一个普遍的、有经验依据的理论。我使用微生物模型系统通过实验来测试进化论的基本理论，这是一种被称为实验进化论的技术。这种方法使我能够实时跟踪多样性的出现和命运，并结合基因组测序，使我能够识别导致适应和多样化的基因变化。这里提出的研究问题是，当面临比以前考虑的更复杂的生态和基因系统时，我们现有的模型在解释适应性多样化模式方面做得有多好。我们的短期目标是(1)评估网络拓扑对元种群适应的影响，以及(2)测试适应度景观的结构--从基因型到适应度的映射--在适应过程中如何变化。更具体地说，我们问空间结构，即通过扩散联系起来的子种群网络，是否会影响在其他相同环境中进行选择的结果。如果环境在空间上也是可变的，从这个意义上说，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演变？适应模型在预测导致适应的基因变化序列方面有多好？这项工作的动机是基础问题，因此将有助于进化、遗传学和生态学的基本知识，并在这笔赠款的过程中培训至少17名高素质的人，从本科生到博士。然而，这项研究的大部分内容是病原微生物的管理，特别是在抗菌素耐药性方面。长期以来，人们一直认识到，我们在治疗传染病方面面临的许多挑战都是以进化为核心的。这项工作是朝着评估进化理论迈出的第一步，进化理论可以为与传染病的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.