The architecture and evolution of host control in a microbial symbiosis

微生物共生中宿主控制的结构和进化

• 批准号: BB/X016439/1
• 负责人: Michael Brockhurst
• 金额: $ 83.81万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX016439%2F1
• 关键词: architecture; evolution; host; control; microbial

Beneficial symbioses are widespread in nature and underpin the function of both natural and manmade ecosystems. Moreover, by providing the interacting species with new ecological functions, symbiosis represents an important source of innovation and has thus played a crucial role in the evolution of life on Earth. In endosymbiosis, endosymbiont cells live within host cells and, as such, hosts have evolved mechanisms to control these endosymbionts, collectively termed "host control". However, despite decades of study, the molecular mechanisms that hosts use to control their endosymbionts remain poorly understood. In particular, how the architecture of host control systems has evolved to provide hosts with sufficient flexibility to respond to changing conditions whilst also being evolutionarily robust is unknown for any symbiosis. Experimental studies of these questions in many symbioses are challenging because symbiotic organisms are not easily cultured independently nor typically amenable to genetic manipulation. In this project we overcome these challenges by using an experimentally tractable microbial symbiosis between the single-celled ciliate host Paramecium and the green alga Chlorella for which we have developed tools to "knockdown" the expression of target genes. In this symbiosis, hosts exchange nitrogen compounds derived from heterotrophy for carbohydrates from algal photosynthesis. In previous work we discovered that hosts modulate the number of algal symbionts in response to light intensity to maximise their fitness gains, but how hosts exert this control is not clear. In preliminary experiments for this proposal, we have discovered two putative mechanisms of host control, combining both positive and negative control levers, that hosts appear to use to regulate the number of algal symbionts per host cell. We predict that such multi-layered host control enables more precise regulation of endosymbiont number across environmental gradients whilst also providing a degree of redundancy so that the system has greater evolutionary robustness. To test these ideas, we will perform "gene knockdown" experiments to disrupt either each individual or both host control mechanisms and measure how this affects host growth, plasticity and fitness. Using cutting edge molecular methods, we will discover how each of the host control mechanisms works through understanding their effect on gene regulation and metabolism in both the host and symbiont. Finally, we will use experimental evolution to discover how the symbiosis recovers from disruption of host control systems, and test whether multiple layers of control enhance evolutionary robustness. Together these experiments will advance our understanding of the biology of symbioses, helping to solve the long-standing evolutionary puzzle of how and why symbioses evolve. In so doing the research will also provide insight into how symbioses and the important functions they perform can be maintained in natural and man-made ecosystems.

有益的共生现象在自然界广泛存在，是自然和人造生态系统功能的基础。此外，通过为相互作用的物种提供新的生态功能，共生是创新的重要来源，因此在地球上生命的进化中发挥了至关重要的作用。在内共生中，内共生细胞生活在宿主细胞内，因此，宿主进化出了控制这些内共生细胞的机制，统称为“宿主控制”。然而，尽管经过了几十年的研究，宿主用来控制其内共生体的分子机制仍然知之甚少。特别是，宿主控制系统的架构如何进化到为宿主提供足够的灵活性来应对不断变化的条件，同时也具有进化鲁棒性，这对于任何共生都是未知的。在许多共生生物中对这些问题进行实验研究是具有挑战性的，因为共生生物不容易独立培养，也不容易进行遗传操作。在这个项目中，我们通过单细胞纤毛虫宿主草草虫和绿藻小球藻之间的实验处理微生物共生来克服这些挑战，为此我们开发了“敲低”目标基因表达的工具。在这种共生关系中，寄主交换来自异养的氮化合物，以换取藻类光合作用产生的碳水化合物。在之前的研究中，我们发现寄主根据光照强度调节藻类共生体的数量，以最大限度地提高它们的适应性，但寄主如何施加这种控制尚不清楚。在本提案的初步实验中，我们发现了两种假定的宿主控制机制，结合了正控制杠杆和负控制杠杆，宿主似乎使用它们来调节每个宿主细胞的藻类共生体数量。我们预测，这种多层宿主控制能够更精确地调节跨环境梯度的内共生体数量，同时也提供一定程度的冗余，使系统具有更大的进化鲁棒性。为了验证这些想法，我们将进行“基因敲低”实验，破坏每个个体或两个宿主的控制机制，并测量这如何影响宿主的生长、可塑性和适应性。利用尖端的分子方法，我们将通过了解它们对宿主和共生体的基因调控和代谢的影响，发现每种宿主控制机制是如何工作的。最后，我们将使用实验进化来发现共生如何从宿主控制系统的破坏中恢复，并测试多层控制是否增强了进化鲁棒性。总之，这些实验将促进我们对共生生物学的理解，帮助解决共生如何以及为什么进化的长期进化难题。这样做的研究也将提供深入了解共生及其在自然和人造生态系统中发挥的重要功能是如何维持的。