Quantifying the genomic sources of evolutionary innovations through integrative biology

快速的环境变化需要分子创新来应对。宏观进化描述了生物如何在地质时间尺度上殖民新的环境。相比之下，我们在基因组水平上对微创新的数量特征知之甚少，即它们对表型和适合度的数量贡献是什么，它们如何首先在种群中发生，以及它们如何被突变、自然选择和遗传漂变所塑造。此外，一般来说，我们可以了解进化过程中发生了什么，但不知道可能发生什么，也就是说，自然选择和随机遗传漂变可以提供什么。我们将在不同的分辨率和不同的时间尺度上研究这些问题，使用向前进化和分析过去的进化。由于酿酒酵母是基因组学、细胞生物学和生理学的核心真核生物模型，因此在希望从基因组转向表型的研究背景下，酿酒酵母属为基因组的操作和分析提供了独特的机会。它们相对较小的基因组和快速的进化使探索进化机制达到饱和，有可能使驱动进化的关键因素完全参数化。我们将在两个时间尺度上讨论基因组的新颖性是如何产生的。在第一种情况下，我们将检查可能比实际碱基对突变率更快发生的极端快速变化，我们认为这是相关的，例如在适应极端条件的背景下，否则会导致灭绝。我们将研究物种如何在种间杂交过程中结合和混合它们的基因组，以推动进化向前发展。在第二种情况下，我们将关注更长的时间尺度，即种群分化并成为物种的尺度。在这个时间尺度上，我们将研究新基因如何从非编码序列中进化到基因组中。最后，我们将研究如何短和长时间尺度的过程可以相互协同。我们将通过分析野外的自然多样性和实验室中进化的基因组和种群来更好地理解这些过程。我们还将利用基因组编辑技术的最新发展，一次一次地研究一个进化变化，新基因等分子新颖性如何进化并导致适应性变化。新颖性和重要性：生物学需要对基因组与表型之间的关系有更好的定量理解。这项研究计划将借鉴最新的技术发展，在这个方向上迈出重要的一步。这将为基因组组织如何在基因型水平上产生新颖性以及这如何影响生物系统及其性能提供坚实的基础。

Background Rapid environmental changes have to be met with molecular innovations. Macroevolution has described how organisms may have colonized new environments over geological time scales. In contrast, we know relatively little about the quantitative features of micro-innovations at the genomic level, i.e. what is their quantitative contribution to phenotypes and fitness, how they first occur in populations and how they are shaped by mutation, natural selection and genetic drift. Moreover, in general, we have access to what happened during evolution but not to what could have happened, i.e. what was available to natural selection and random genetic drift. We will examine these questions at different levels of resolution and at different time scales, using forward evolution and the analysis of evolution back in time. The Study System Because S. cerevisiae has been the core eukaryote model in genomics, cell biology and physiology, the Saccharomyces genus offers a unique opportunity for the manipulation and analysis of genomes in the context of research that wants to navigate from the genome to phenotypes. Their relatively small genomes and rapid evolution allow to explore evolutionary mechanisms to saturation, potentially enabling the full parameterization of the key factors driving evolution. Objectives We will be addressing how novelty comes about in genomes at two time scales. In the first case, we will examine extremely rapid changes that may occur faster than actual base-pair mutation rates, which we think is relevant, for instance in the context of adaptation to extreme conditions that would otherwise lead to extinction. We will examine how species can combine and mix their genomes during inter-species hybridization to propel evolution forward. In the second case, we will focus on a longer time scale, the scale at which populations diverge and become species. In this timescale, we will examine how novel genes evolve in genomes from non-coding sequences. Finally, we will examine how short and long time scale processes can synergize each other. We will gain a better understanding of these processes by analysing natural diversity in the wild and by evolving genomes and populations in the laboratory. We will also harness the latest development in genome editing technologies to examine, one evolutionary change at a time, how molecular novelties such as novel genes evolve and contribute to fitness variation. Novelty and significance: Biology needs a better quantitative understanding of the relationships that link genomes to phenotypes. This research program will draw from the most recent technological developments to provide a major step in this direction. This will provide a strong foundation in terms of how genome organization produces novelty at the genotypic level and how this affects biological systems and their performance.