Rooting the eukaryotic radiation with new models of gene and genome evolution

真核生物起源于它们的原核祖先，是生命历史上最具形成性的转变之一，促进了真核生物多样性的蓬勃发展，形成了我们今天看到的令人惊叹的各种形式，从地球上最大的生物--蓝鲸、巨型红杉、延伸到地下数英里的真菌网络--到与世界海洋中的细菌相互竞争的微型浮游生物。解释原核生物向真核生物转变过程中细胞复杂性的飞跃是21世纪生物学面临的突出挑战之一。所有真核细胞的共同结构证明了它们共同的祖先，但我们对祖先真核生物是哪种细胞-它生活在哪里，吃什么，它可以进行哪种生化反应-的理解是混乱的。全基因组数据使我们能够解决真核生物进化中最近的分歧，但我们仍然对进化树基础上的主要群体之间的更深层次关系了解得很少。尤其是树根--真核生物辐射的起点--仍然存在争议和争论。问题是，传统的生根方法依赖于外群的使用：例如，为了找到哺乳动物树根，我们可能会将鸟类包括在分析中，然后使用我们的先验知识将根放置在两个组之间的树枝上。当应用于真核辐射时，这种方法就失效了：包括我们最接近的原核近亲，极大地减少了可分析的真核基因组的比例，而与原核外群的巨大进化距离掩盖了不同真核谱系之间的关系。因此，尽管使用了相似的数据集和分析方法，但最近对真核植物根的分析在其位置上存在强烈分歧。在这个项目中，我们将正面解决这些困难，通过应用新的无外群生根方法来最终解决真核树的根，其中包括项目组成员开创的一些方法，以获得迄今组装的最新的、具有代表性的真核基因组多样性样本。我们将使用由此产生的系统基因组框架来绘制进化史上现代真核生物独特的细胞和基因组特征首次进化的时间点，为真核生物关键创新的进化建立一个时间表。通过将这些特征映射到树上，我们将重建祖先真核生物-一种可能生活在20亿年前的有机体-的详细细胞和基因组模型，以确定其生活方式、生态和新陈代谢，并测试关于原始谱系如何导致我们今天看到的真核生物惊人多样性的假说。我们正在提议的工作是基础发现科学：最终目标是了解我们自己的起源，澄清生命历史上一个鲜为人知的时期，这对于理解我们今天看到的生物多样性至关重要，并通过这样做来建立一个新的最先进的系统发生学根源，广泛适用于整个生命树的其他重大进化转变。但也有可能产生更广泛的社会经济影响。真核树底部附近的一些种群是寄生的，因此确定这些种群是如何从它们自由生活的祖先进化而来的，将为锥虫(昏睡病)和贾第鞭毛虫等真核寄生虫对宿主的适应提供新的、亟需的见解。作为研究计划的一部分，我们将为有动力的学生举办生物黑客(DIY计算生物学)的暑期实习，提供科学发现的滋味，并教授识别和培养下一代科学领袖所需的关键计算、统计和科学技能。

The origin of eukaryotes from their prokaryotic progenitors was one of the most formative transitions in the history of life, catalysing the blossoming of eukaryotic biodiversity into the astonishing range of forms we see today, from the largest organisms on our planet - blue whales, giant sequoias, fungal networks extending for miles underground - to microscopic plankton that jostle with bacteria in the world's oceans. Explaining the leap in cellular complexity during the prokaryote-to-eukaryote transition is one of the outstanding challenges in 21st-century biology.The common structure of all eukaryotic cells testifies to their shared ancestry, but our understanding of the kind of cell that ancestral eukaryote was - where it lived, what it ate, the kinds of biochemical reactions it could perform - is in disarray. Whole-genome data have enabled us to resolve the more recent divergences in eukaryotic evolution, but we still have a very poor understanding of the deeper relationships between the main groups at the base of the evolutionary tree. In particular, the root of the tree - the starting point of the eukaryotic radiation - remains mired in controversy and debate.The problem is that traditional rooting methods rely on the use of an outgroup: to find the root of the tree of mammals, for example, we might include birds in the analysis, and then use our a priori knowledge to place the root on the branch between the two groups. This approach breaks down when applied to the eukaryotic radiation: including our closest prokaryotic relatives greatly reduces the proportion of the eukaryotic genome that can be analysed, and the enormous evolutionary distance to the prokaryotic outgroup obscures the relationships among the different eukaryotic lineages. As a result, recent analyses of the eukaryotic root disagree strongly on its position, despite using similar datasets and analytical approaches. In this project, we will tackle these difficulties head-on to definitively resolve the root of the eukaryotic tree by applying new outgroup-free rooting approaches, including some pioneered by members of the project team, to the most up-to-date, representative sampling of eukaryotic genomic diversity yet assembled. We will use the resulting phylogenomic framework to map the points in evolutionary history at which the unique cellular and genomic traits of modern eukaryotes first evolved, establishing a timescale for the evolution of key eukaryotic innovations. By mapping these traits onto the tree, we will reconstruct a detailed cellular and genomic model of the ancestral eukaryote - an organism which may have lived up to two billion years ago - in order to establish its lifestyle, ecology, and metabolism, and to test hypotheses of how that founding lineage gave rise to the staggering diversity of eukaryotic life we see today. The work we are proposing is fundamental discovery science: the ultimate goal is to understand our own origins, to bring clarity to a poorly-understood period in the history of life vitally important for making sense of the biodiversity we see around us today, and in doing so to establish a new state-of-the-art for phylogenetic rooting with broad applicability to other major evolutionary transitions across the tree of life. But there is also real potential for broader socio-economic impact. Some of the groups that branch near the base of eukaryotic tree are parasitic, and so establishing how these evolved from their free-living ancestors will provide new, much-needed insights into the adaptation of eukaryotic parasites such as Trypanosoma (sleeping sickness) and Giardia to their hosts. As part of the research programme, we will host summer internships for motivated students on biohacking (DIY computational biology), providing a taste of scientific discovery and teaching the crucial computational, statistical and scientific skills needed to identify and nurture the next generation of scientific leaders.