The role of a mysterious epigenetic RNA modification in adapting the eukaryotic epitranscriptome to environmental change

生物如何响应和适应不断变化的环境仍然是生态学和进化中最重要的问题。气候变化和人类活动给生物体带来了前所未有的压力。个体生物必须通过调节基因表达和蛋白质来快速调整其生理机能，这为自然选择提供了原材料，从而在种群和物种水平上赋予长期适应能力。表观遗传学是生物体对环境变化作出快速反应的重要机制。DNA甲基化就是这样一个影响基因表达的过程，并为自然选择提供分子多样性。然而，mRNA而非DNA的表观遗传修饰可能是一个比DNA甲基化更重要的过程，它可以比DNA甲基化更快速、更灵活地产生分子多样性。因此，确定这种“表转录组”RNA修饰的原因和后果对于理解和预测分子进化至关重要。一个特别有趣的RNA修饰是剪接先导反式剪接（SLTS）。这个过程在一些真核mrna的5'端增加了一个短核苷酸基序。这个基序没有被翻译，但它的存在可能对mRNA加工产生影响，最终可能影响生物体的生理和生态表型。人们对SLTS知之甚少，并且仅在有限数量的生物体中有零星的特征。因此，我们对SLTS的进化史及其在生物体对环境因素作出反应中的作用知之甚少。在这个项目中，学生将首先利用我们实验室开发的计算管道和公开可用的测序数据来解决令人兴奋的问题，例如：SLTS在整个真核生命树中有多普遍？SLTS频率在不同谱系之间有何差异？SLTS是否在系统发育独立的谱系中平行进化？然后，学生将在我们实验室建立的无脊椎动物（例如，海洋甲壳类动物，藻类或线虫）上进行压力实验，从野外种群中收集样本，并使用最先进的RNA和DNA测序技术（牛津纳米孔MinION）来确定：实验处理对全基因组SLTS模式的影响。野外样品中SLTS模式的空间结构。SLTS模式与遗传/表观遗传多样性的关系。现代生物学是越来越多的跨学科，依靠计算数据分析和传统的实地考察和实验室为基础的技能。该项目将提供所有这些方面的培训，这种结合在学术和工业职业轨道上都受到高度追捧。

How organisms respond and adapt to ever-changing environments remains a most critically important question in ecology and evolution. Climate change and human activity are causing unprecedented pressures onto organisms to cope with stresses. Individual organisms must rapidly adjust their physiology by modulating gene expression and protein repertoires, which provide raw material for natural selection to confer long-term adaptation on a population and species level. Epigenetics is a crucial mechanism through which organisms may respond rapidly to environmental change. DNA methylation is one such process that affects gene expression and provides molecular diversity for natural selection to act on. However, epigenetic modification of mRNA instead of DNA may be an even more important process that could generate molecular diversity more rapidly and flexibly than DNA methylation. Therefore, identifying the causes and consequences of such "epitranscriptomic" RNA modifications is critically important for understanding and predicting molecular evolution. A particularly intriguing RNA modification is spliced leader trans-splicing (SLTS). This process adds a short nucleotide motif to the 5'-end of some eukaryotic mRNAs. This motif is not translated but its presence may have effects on mRNA processing that may ultimately affect the physiological and ecological phenotype of the organism. SLTS is poorly understood and only patchily characterised in a limited number of organisms. Therefore, we know very little about the evolutionary history of SLTS and its role in allowing organisms to respond to environmental factors. In this project, the student will first capitalise on computational pipelines that our lab developed and publicly available sequencing data to address exciting questions such as: How common is SLTS throughout the eukaryotic tree of life? How does SLTS frequency vary among lineages? Did SLTS evolve in parallel in phylogenetically independent lineages? The student will then carry out stress experiments on invertebrates established in our labs (for example, marine crustaceans, algae or nematodes), collect samples from field populations, and use state-of-the-art RNA and DNA sequencing technologies (Oxford NanoPore MinION) to identify: Effects of experimental treatments on genome-wide SLTS patterns. Spatial structure of SLTS patterns in field samples. Relationships between patterns of SLTS and genetic/epigenetic diversity. Modern biology is increasingly interdisciplinary, relying on computational data analysis and traditional fieldwork and lab-based skills. This project will provide training in all these aspects, a combination that is highly sought after in both academic and industrial career tracks.