Microevolution in the pansecondary metabolome of Aspergillus flavus and its potential macroevolutionary implications for filamentous fungi
Microevolution in the pansecondary metabolome of Aspergillus flavus and its potential macroevolutionary implications for filamentous fungi
复制标题
DOI：
10.1073/pnas.2021683118
复制
发表时间：
2021-05-25
影响因子：
11.1
通讯作者：
Keller, Nancy P.
中科院分区：
文献类型：
--
作者：
Drott, Milton T.;Rush, Tomas A.;Keller, Nancy P.
真菌通过生物合成基因簇（BGC）产生大量具有生物活性的次级代谢产物（SM）。药物发现工作的常见做法是将物种的次级代谢组视为由单个或少量代表性基因组很好地代表。然而，这种方法错过了种内种群动态的可能性，如适应环境条件或当地微生物组，可能窝藏新的BGC，有助于物种的整体生态位宽度。使用从美国七个州采样的94株世界性模式真菌黄曲霉菌株，我们将7，821个BGC复制成92个独特的BGC。我们发现，超过25%的泛基因组BGC显示存在/不存在或蛋白质分歧的群体特异性模式。种群特异性BGC构成了大多数的辅助基因组BGC，这表明维持辅助基因组的不同生态力可能部分由次级代谢的种群特异性差异介导。我们使用超高性能高分辨率质谱来证实BGC中的这些遗传差异也导致不同群体中SM生产的化学型差异，这可能介导生态相互作用并通过选择作用。因此，我们的研究结果表明，以前未实现的人口水平水库SM多样性的范式转变，可能是显着的进化，生态和药理学的重要性。最后，我们发现了几个来自A.黄曲霉中存在的寄生曲霉和曲霉minisclerotigenes，并讨论如何微进化模式，我们发现通知宏观进化推论，并帮助调整真菌次生代谢与现有的进化理论。
Fungi produce a wealth of pharmacologically bioactive secondary metabolites (SMs) from biosynthetic gene clusters (BGCs). It is common practice for drug discovery efforts to treat species' secondary metabolomes as being well represented by a single or a small number of representative genomes. However, this approach misses the possibility that intraspecific population dynamics, such as adaptation to environmental conditions or local microbiomes, may harbor novel BGCs that contribute to the overall niche breadth of species. Using 94 isolates of Aspergillus flavus, a cosmopolitan model fungus, sampled from seven states in the United States, we dereplicate 7,821 BGCs into 92 unique BGCs. We find that more than 25% of pangenomic BGCs show population-specific patterns of presence/absence or protein divergence. Population-specific BGCs make up most of the accessory-genome BGCs, suggesting that different ecological forces that maintain accessory genomes may be partially mediated by population-specific differences in secondary metabolism. We use ultra-high-performance high-resolution mass spectrometry to confirm that these genetic differences in BGCs also result in chemotypic differences in SM production in different populations, which could mediate ecological interactions and be acted on by selection. Thus, our results suggest a paradigm shift that previously unrealized population-level reservoirs of SM diversity may be of significant evolutionary, ecological, and pharmacological importance. Last, we find that several population-specific BGCs from A. flavus are present in Aspergillus parasiticus and Aspergillus minisclerotigenes and discuss how the microevolutionary patterns we uncover inform macroevolutionary inferences and help to align fungal secondary metabolism with existing evolutionary theory.