The pan-genome of Aspergillus fumigatus provides a high-resolution view of its population structure revealing high levels of lineage-specific diversity driven by recombination.
The pan-genome of Aspergillus fumigatus provides a high-resolution view of its population structure revealing high levels of lineage-specific diversity driven by recombination.
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DOI：
10.1371/journal.pbio.3001890
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发表时间：
2022-11
期刊：
影响因子：
9.8
通讯作者：
中科院分区：
文献类型：
--
作者：
烟曲霉是一种致命的人类真菌性疾病，其中毒力异质性被认为至少部分是由菌株之间的遗传变异构成的。虽然基于参考基因组比对的群体基因组分析提供了对基因变异如何在群体中分布的有价值的见解，但这些方法未能捕获参考基因组中不存在的基因的种内变异。基于从头组装的泛基因组分析为基于参考的基因组学提供了一种有前途的替代方案，具有解决物种全部遗传库的潜力。在这里，我们评估了260个A.烟曲霉包括62个新测序的菌株，使用人口基因组学，基因组学和泛基因组学的组合。我们的研究结果提供了一个高分辨率的人口结构和重组频率，遗传结构的基因存在-不存在的变化，代谢特异性的证据，和分布的假定抗真菌药物耐药基因的评估。虽然A.虽然烟曲霉主要通过无性分生孢子分散，但我们鉴定出了非常高水平的重组，其中迄今为止报道的任何真菌物种的连锁不平衡衰减值最低。我们提供了证据，3个主要群体的A。fumigatus，重组很少发生在种群之间，往往在它们内部。这3个群体的结构都是由基因变异和独特的模式，基因的存在，不存在与独特的套件的辅助基因目前专门在每个分支。辅助基因显示功能丰富的氮和碳水化合物的代谢，表明人口可能分层的环境生态位专业化。同样，抗真菌药物的耐药基因和耐药等位基因的分布往往是由遗传结构。总的来说，A.烟曲霉代表了迄今为止报道的最大的真菌泛基因组之一，包括Af 293参考基因组中未呈现的许多基因。这些结果强调了依赖于单一参考基因组为基础的方法来评估种内变异的不足，以及组合基因组方法来阐明临床相关真菌的种群结构、遗传多样性和推定的生态驱动因素的能力。一个组合的人口基因组学，基因组学和泛基因组学的方法揭示了高水平的重组和代谢多样性的证据，在机会真菌病原体烟曲霉。
Aspergillus fumigatus is a deadly agent of human fungal disease where virulence heterogeneity is thought to be at least partially structured by genetic variation between strains. While population genomic analyses based on reference genome alignments offer valuable insights into how gene variants are distributed across populations, these approaches fail to capture intraspecific variation in genes absent from the reference genome. Pan-genomic analyses based on de novo assemblies offer a promising alternative to reference-based genomics with the potential to address the full genetic repertoire of a species. Here, we evaluate 260 genome sequences of A. fumigatus including 62 newly sequenced strains, using a combination of population genomics, phylogenomics, and pan-genomics. Our results offer a high-resolution assessment of population structure and recombination frequency, phylogenetically structured gene presence–absence variation, evidence for metabolic specificity, and the distribution of putative antifungal resistance genes. Although A. fumigatus disperses primarily via asexual conidia, we identified extraordinarily high levels of recombination with the lowest linkage disequilibrium decay value reported for any fungal species to date. We provide evidence for 3 primary populations of A. fumigatus, with recombination occurring only rarely between populations and often within them. These 3 populations are structured by both gene variation and distinct patterns of gene presence–absence with unique suites of accessory genes present exclusively in each clade. Accessory genes displayed functional enrichment for nitrogen and carbohydrate metabolism suggesting that populations may be stratified by environmental niche specialization. Similarly, the distribution of antifungal resistance genes and resistance alleles were often structured by phylogeny. Altogether, the pan-genome of A. fumigatus represents one of the largest fungal pan-genomes reported to date including many genes unrepresented in the Af293 reference genome. These results highlight the inadequacy of relying on a single-reference genome-based approach for evaluating intraspecific variation and the power of combined genomic approaches to elucidate population structure, genetic diversity, and putative ecological drivers of clinically relevant fungi. A combined population genomics, phylogenomics, and pan-genomics approach reveals evidence for high levels of recombination and metabolic diversity in the opportunistic fungal pathogen Aspergillus fumigatus.
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DOI：
10.1016/j.fgb.2018.02.003
发表时间：
2018-04
期刊：
Fungal genetics and biology : FG & B
影响因子：
--
作者：
Ballard E;Melchers WJG;Zoll J;Brown AJP;Verweij PE;Warris A
通讯作者：
Warris A
DOI：
10.3390/jof4010039
发表时间：
2018-03-20
期刊：
Journal of fungi (Basel, Switzerland)
影响因子：
--
作者：
Basenko EY;Pulman JA;Shanmugasundram A;Harb OS;Crouch K;Starns D;Warrenfeltz S;Aurrecoechea C;Stoeckert CJ Jr;Kissinger JC;Roos DS;Hertz-Fowler C
通讯作者：
Hertz-Fowler C
影响因子：
4.9
作者：
Bao W;Kojima KK;Kohany O
通讯作者：
Kohany O
影响因子：
5.2
作者：
Annick Ries, Laure Nicolas;Steenwyk, Jacob L.;Goldman, Gustavo H.
通讯作者：
Goldman, Gustavo H.
影响因子：
3.4
作者：
Mafu, Akier Assanta;Plumety, Corinne;Goulet, Jacques
通讯作者：
Goulet, Jacques