High-resolution genotype-phenotype map of speciation and adaptation

了解突变、随机遗传漂移和自然选择如何与生态因素相互作用来推动进化是生物学中最大的挑战之一。实现这一目标需要我们了解基因的变化如何导致表型的变化。这种从基因型到表型的映射涉及在基因(DNA)和适合度之间绘制中间水平(转录本、蛋白质、代谢物、细胞网络)的表型变化及其潜在分子基础之间的机制联系。基因类型转化为表型的机制本身，以及突变和自然选择等进化力量，是什么解决方案可能和将在进化过程中使用的主要决定因素。我的目标是研究基因组和细胞网络在进化过程中如何变化，以及细胞网络的架构本身如何在与环境变化的相互作用中影响进化过程。我将通过结合两种方法来实现这一目标。第一个是前瞻性的，将使用实验进化。我将测试关于蜂窝网络结构在塑造适应和物种形成中的作用以及适应和物种形成在塑造细胞网络中的作用的假设。我的模型系统将是萌芽酵母酿酒酵母，这是系统和细胞生物学中最先进的模型系统。第二种方法是追溯性。我将开发一个适应和物种形成的模式系统，这是我们最近在野外发现的，萌芽酵母Sparoxus，它是模式酿酒酵母的姐妹物种。这一物种与细胞网络被广泛描述的模型密切相关。我将使用这个系统来绘制自然界中适应和生殖隔离的遗传决定因素，并将涉及的基因映射到酵母细胞网络上。将分子水平上描述良好的生物与进化研究相结合的能力将带来普通生态学和进化界以及细胞生物学界无法获得的结果。我的研究将一)阐明我们对通过进化出现复杂生物系统和功能的理解；二)预测生物多样性的进化将如何应对全球环境变化；三)允许预测和控制动植物科学的进化，例如细菌和真菌中的抗生素耐药性。最后，了解蜂窝网络体系结构如何影响进化将使人们能够在生物技术的背景下使用进化原理来构建服务于人类未来和可持续发展的工具和有机体。

Understanding how mutations, random genetic drift and natural selection interact with ecological factors to drive evolution is one of the greatest challenges in biology. Achieving this goal requires that we understand how changes in genes lead to changes in phenotypes. This genotype-to-phenotype mapping involves drawing mechanistic links between phenotypic changes and their underlying molecular bases at intermediate levels (transcripts, proteins, metabolites, cellular networks) between the genotype (DNA) and fitness. The mechanisms by which genotypes are translated into phenotypes is itself, along with evolutionary forces such as mutation and natural selection, a major determinant of what solutions are possible and will be used during evolution. My objective is to examine how genomes and cellular networks change during evolution and how the architecture of cellular networks can itself influence the course of evolution in interaction with environmental changes. I will reach this objective by combining two approaches. The first one is prospective and will use experimental evolution. I will test hypotheses regarding the role of cellular network architecture in shaping adaptation and speciation and the role of adaptation and speciation in shaping cellular networks. My model system will be the budding yeast Saccharomyces cerevisiae, the most advanced model system in systems and cell biology. The second approach is retrospective. I will exploit a model system for adaptation and speciation that we recently discovered in the wild, the budding yeast S. paradoxus, which is the sister species of the model S. cerevisiae. S. paradoxus offers a unique opportunity to study adaptation and speciation in the wild in a species that is very closely related to a model for which cellular networks are extensively described. I will use this system to map the genetic determinants of adaptation and reproductive isolation in nature and map the genes involved onto the yeast cellular network. The ability to combine well described organisms at the molecular level with evolutionary studies will bring findings that have not been accessible to the general ecology and evolution community nor to the cell biology community. My research will i) illuminate our understanding of the emergence of complex biological systems and functions through evolution; ii) make possible predictions on how the evolution of biodiversity will proceed in response to global environmental changes and iii) allow forecasting and controlling evolution in animal and plant sciences, such as in the case of antibiotic resistance in bacteria and fungi. Finally, learning on how cellular network architecture influences evolution will enable the use of evolutionary principles in the context of biotechnologies to build tools and organisms that will serve Human's future and sustainable development.