Cross-kingdom health: evolution of innate immune receptors and their targets

项目总结 来自NLR蛋白家族的先天免疫受体控制着基本的生物体-生物体相互作用 王国，包括物种内的不相容。目前基因组生物多样性的可用性使得 我们将研究先天免疫受体进化的模式。我认为获得性免疫已经进化 通过采用先天免疫中已经存在的蛋白质结构域的子集以及它们的多样性 在特化细胞中发挥躯体作用的机制。通过比较基因组学检验这一假说 将改变我们对免疫系统进化的理解。为此，我们将检查 涉及天然免疫的蛋白质结构域在所有可用的真核基因组中的进化， 确定基因组多样性的来源以及它们如何随着适应性的重新进化而变化 独立血统的豁免权。测试是否存在有针对性的多样性生成机制 在种群水平上，我们将研究NLR在多个尺度上的演变模式， 包括跨领域的分析。我们将在物种内部测试作用于它们的多样化机制 缺乏适应性免疫，包括模式植物和真菌。同时，我们将在实验中测试 NLRs参与真菌免疫，这一点已经提出，但尚未得到实验验证。 最后，我们将对NLR及其配体进行实验进化，以收集数据用于建模 如何在人口规模上产生新的约束性特征。总而言之，这个项目将填补重要的 在理解包括我们自己在内的先天免疫系统的进化方面存在差距。

PROJECT SUMMARY Innate immune receptors from the NLR protein family control basic organism-organism interactions across kingdoms, including incompatibility within a species. Current availability of genomic biodiversity allows us to examine patterns of innate immune receptor evolution. I propose that adaptive immunity has evolved by adopting subsets of proteins domains already present in innate immunity as well as their diversification mechanisms to act somatically in specialized cells. Testing this hypothesis through comparative genomics will be paradigm-shifting to our understanding of immune system evolution. To do this, we will examine evolution of protein domains involved in innate immunity across all available eukaryotic genomes, determine sources of genomic diversity and how they change with the re-current evolution of adaptive immunity across independent lineages. To test that there are targeted diversity generation mechanisms acting on NLRs at the population level, we will examine patterns of NLR evolution on multiple scales, including cross-kingdom analyses. We will test diversification mechanisms acting on them within species lacking adaptive immunity, including model plants and fungi. In parallel, we will experimentally test involvement of NLRs in fungal immunity, which has been proposed but yet to be experimentally validated. Finally, we will conduct experimental evolution on both NLRs and their ligands to collect data for modeling how new binding specificities arise on the population scale. Altogether, this project will fill in important gaps in understanding the evolution of innate immune systems, including our own.