Evolutionary models for a changing world

随着物种面临越来越多的人类改变的世界和不断演变的大流行，进化分析和建模的必要性从未像现在这样明确，这一领域对训练有素的HQP的需求非常大。在这个提案中，我概述了如果由NSERC资助，我的团队将完成的理论和实验研究，重点放在三个主要主题上：目标I：进化理论在不断变化的世界中理解生物多样性进化理论使我们能够探索生物系统本身是如何进化的。从根本上说，定义有机体如何生活和繁殖的特征是如何演变的？反过来，这些特征如何决定物种是否以及如何适应不断变化的世界？这些问题是我长期研究兴趣的基础，也是几个HQP项目的重点。我们目前正在研究多个理论项目，这些项目已经产生了新的见解。其中包括探索在变化的环境中进化的模型，通过杂交适应的模型，以及通过拮抗选择长期保持变异的模型。这些只是我们将在NSERC上完成的几个数学和计算项目的例子。目标二：在快速变化的环境中的进化人类在一个世纪内改变地球的速度对单一物种来说是史无前例的。我的研究小组使用酵母来更好地了解在快速变化的环境中进化的潜力和局限性。一个主要问题是，对于进化适应来说，哪些环境组合特别具有挑战性，哪些环境组合特别容易。我们的实验室将量化酵母适应金属污染物的能力，确定耐药的遗传机制，并评估对其他金属的交叉耐药。这项工作将提供关于哪些金属组合对适应特别具有挑战性的信息，并将深入了解交叉抗性的遗传机制，这可能有助于修复受污染的地点。目标三：不断演变的大流行自SARS-CoV-2首次出现以来，我的团队一直参与对新冠肺炎的建模，从各种政策选择的影响到塑造该病毒的选择性压力。我们已经并将继续为社会服务，进行相关和及时的建模。除了与政策相关的模型外，我还试图澄清选择如何对SARS-CoV-2起作用的基本方面。一个有争议的方面是，进化在多大程度上是由个体内部的选择压力决定的，而不是个体之间的。我的团队将开发模型，解释病毒在个体内复制和在个体之间传播时突变的传播，以阐明在每个水平上选择的相对重要性。我们还将开发新的理论来指导行动，使其在不同的人群中最有效。我们还在开发新的方法来寻找潜在关注的重组体，更早地识别新的变异体，并估计这些变异体的选择。

With species facing an increasingly human-altered world and an evolving pandemic, the need for evolutionary analyses and modelling has never been clearer, with great demand for well trained HQP in this area. In this proposal, I outline the theoretical and experimental research that my group will accomplish if funded by NSERC, focusing on three major themes: Goal I: Evolutionary Theory to Understand Biodiversity in a Changing World Evolutionary theory allows us to probe how the biological system itself evolves. Fundamentally, how do the features evolve that define how an organism lives and reproduces? In turn, how do those features determine whether and how species adapt in a changing world? These questions underlie my long-term research interests and are the focus of several HQP projects. We are currently investigating multiple theory projects, which are already yielding novel insights. Among these are models exploring evolution in changing environments, adaptation with hybridization, and the long-term maintenance of variation with antagonistic selection. These are just a few examples of mathematical and computational projects that we will complete over this NSERC. Goal II: Evolution in a Rapidly Changing Environment Humans have altered the planet at a speed undocumented for a single species in a single century. My research group uses yeast to better understand the potential and limits of evolution in a rapidly changing environment. One major question is which combinations of environments are particularly challenging, and which easy, for evolutionary adaptation. Our lab will quantify the ability of yeast to adapt to metal pollutants, determine the genetic mechanisms of resistance, and assess cross-resistance to other metals. This work will provide information about which combinations of metals are particularly challenging for adaptation and will give insight into the genetic mechanisms of cross-resistance that might help remediate polluted sites. Goal III: An Evolving Pandemic My group has been involved in modelling COVID-19 since SARS-CoV-2 first arose, from the impact of various policy options to the selective pressures shaping the virus. We have and will continue to be at the service of society to conduct relevant and timely modelling. In addition to policy-relevant models, I have sought to clarify fundamental aspects of how selection acts on SARS-CoV-2. One controversial aspect is how much evolution is shaped by selective pressures within versus between individuals. My group will develop models that account for the spread of mutations as the virus replicates within and transmits among individuals to clarify the relative importance of selection at each level. We will also develop new theory to guide actions to where they would be most effective within a heterogeneous population. We are also developing new methods to search for recombinants of potential concern, to identify new variants earlier, and to estimate selection on these variants.