Laboratory of Evolutionary Genetics, Institute of Biology, University of Neuchâtel, 2000, Neuchâtel, Switzerland.
Present Address: Institute of Phytopathology, Christian-Albrecht University of Kiel, 24118, Kiel, Germany.
BMC Biol. 2022 Oct 8;20(1):224. doi: 10.1186/s12915-022-01422-z.
Fungi produce a wide range of specialized metabolites (SMs) involved in biotic interactions. Pathways for the production of SMs are often encoded in clusters of tightly arranged genes identified as biosynthetic gene clusters. Such gene clusters can undergo horizontal gene transfers between species and rapid evolutionary change within species. The acquisition, rearrangement, and deletion of gene clusters can generate significant metabolome diversity. However, the genetic basis underlying variation in SM production remains poorly understood.
Here, we analyzed the metabolite production of a large population of the fungal pathogen of wheat, Zymoseptoria tritici. The pathogen causes major yield losses and shows variation in gene clusters. We performed untargeted ultra-high performance liquid chromatography-high resolution mass spectrometry to profile the metabolite diversity among 102 isolates of the same species. We found substantial variation in the abundance of the detected metabolites among isolates. Integrating whole-genome sequencing data, we performed metabolite genome-wide association mapping to identify loci underlying variation in metabolite production (i.e., metabolite-GWAS). We found that significantly associated SNPs reside mostly in coding and gene regulatory regions. Associated genes encode mainly transport and catalytic activities. The metabolite-GWAS identified also a polymorphism in the 3'UTR region of a virulence gene related to metabolite production and showing expression variation.
Taken together, our study provides a significant resource to unravel polymorphism underlying metabolome diversity within a species. Integrating metabolome screens should be feasible for a range of different plant pathogens and help prioritize molecular studies.
真菌产生广泛的参与生物相互作用的特殊代谢物（SMs）。SMs 的产生途径通常编码在紧密排列的基因簇中，这些基因簇被鉴定为生物合成基因簇。这些基因簇可以在物种之间发生水平基因转移，并在物种内发生快速进化变化。基因簇的获得、重排和缺失可以产生显著的代谢组多样性。然而，SM 产生变异的遗传基础仍知之甚少。
在这里，我们分析了小麦病原菌禾谷丝核菌的一个大种群的代谢产物生产。该病原体导致产量大幅下降，并表现出基因簇的变异。我们进行了非靶向超高效液相色谱-高分辨率质谱分析，以分析 102 个相同物种分离株的代谢物多样性。我们发现分离株之间检测到的代谢物丰度存在很大差异。整合全基因组测序数据，我们进行了代谢产物全基因组关联作图，以鉴定代谢产物产生变异的基因座（即代谢产物-GWAS）。我们发现，与代谢物产生相关的显著关联 SNP 主要位于编码区和基因调控区。相关基因主要编码运输和催化活性。代谢物-GWAS 还鉴定了一个与代谢产物产生相关的毒力基因的 3'UTR 区域的多态性，该基因表现出表达变异。
总之，我们的研究为揭示物种内代谢组多样性的遗传多态性提供了重要资源。整合代谢组筛选应该适用于一系列不同的植物病原体，并有助于确定分子研究的优先级。
