Genomic islands in the pathogenic filamentous fungus Aspergillus fumigatus.
Genomic islands in the pathogenic filamentous fungus Aspergillus fumigatus.
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DOI：
10.1371/journal.pgen.1000046
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发表时间：
2008-04-11
期刊：
影响因子：
4.5
通讯作者：
Nierman WC
中科院分区：
文献类型：
--
作者：
Fedorova ND;Khaldi N;Joardar VS;Maiti R;Amedeo P;Anderson MJ;Crabtree J;Silva JC;Badger JH;Albarraq A;Angiuoli S;Bussey H;Bowyer P;Cotty PJ;Dyer PS;Egan A;Galens K;Fraser-Liggett CM;Haas BJ;Inman JM;Kent R;Lemieux S;Malavazi I;Orvis J;Roemer T;Ronning CM;Sundaram JP;Sutton G;Turner G;Venter JC;White OR;Whitty BR;Youngman P;Wolfe KH;Goldman GH;Wortman JR;Jiang B;Denning DW;Nierman WC
我们展示了重要人类病原体烟曲霉 A1163 的新临床分离株以及两种密切相关但很少致病的物种 Neosartorya fischeri NRRL181 和曲霉 clavatus NRRL1 的基因组序列。对 A1163 与最近测序的烟曲霉分离株 Af293 进行比较基因组分析，确定了每个基因组中的核心基因、可变基因和最多 2% 的独特基因。虽然核心基因在核苷酸水平上具有 99.8% 的同一性，但可变基因的同一性可能低至 40%。最分歧的基因座似乎包含与真菌程序性细胞死亡相关的异核不相容（het）基因，例如发育调节因子 rosA。跨物种比较表明，烟曲霉、费氏烟花和棒曲霉的基因分别有8.5%、13.5%和12.6%是物种特异性的。这些基因的大小明显小于核心基因，包含较少的外显子并表现出亚端粒偏向。它们大多数聚集在 13 个染色体岛中，这些岛富含假基因、转座子和其他重复元件。至少 20% 的烟曲霉特异性基因似乎具有功能，并参与碳水化合物和几丁质分解代谢、运输、解毒、次生代谢和其他可能促进适应异质环境（如土壤或哺乳动物宿主）的功能。与之前的建议相反，它们的起源不能归因于水平基因转移（HGT），而可能涉及复制、多样化和差异基因丢失（DDL）。基因组岛的发现进一步强调了复制在谱系特异性基因起源中的作用，这些岛似乎起到指定的“基因转储”的作用，也许同时也起到“基因工厂”的作用。 曲霉属是一种极其多样化的丝状子囊菌真菌（霉菌）属，普遍存在于土壤和腐烂的植被中。作为超级机会主义者，曲霉已经适应克服异质环境中发现的各种化学、物理和生物压力。虽然该属中的大多数物种都是腐生菌，但令人惊讶的是，有很多物种能够感染受伤的植物和动物。值得注意的是，过敏的人类宿主对患有肺部和鼻窦疾病的曲霉菌也有异常反应。免疫抑制剂的出现和其他医学进步已经在全球范围内创造了大量易受某些曲霉属物种影响的人类宿主，其中包括世界上最有害的霉菌和侵袭性曲霉病的病原体烟曲霉。在这项研究中，我们利用比较基因组学的力量来深入了解可能有助于这种重要人类病原体的代谢多功能性和致病性的遗传机制。对两个烟曲霉临床分离株和两个密切相关但很少致病的物种的基因组进行比较表明，它们的基因组包含几个大的分离株和物种特异性染色体岛。这些高度不稳定区域编码的代谢能力可能有助于它们快速适应异质环境，例如土壤或活宿主。
We present the genome sequences of a new clinical isolate of the important human pathogen, Aspergillus fumigatus, A1163, and two closely related but rarely pathogenic species, Neosartorya fischeri NRRL181 and Aspergillus clavatus NRRL1. Comparative genomic analysis of A1163 with the recently sequenced A. fumigatus isolate Af293 has identified core, variable and up to 2% unique genes in each genome. While the core genes are 99.8% identical at the nucleotide level, identity for variable genes can be as low 40%. The most divergent loci appear to contain heterokaryon incompatibility (het) genes associated with fungal programmed cell death such as developmental regulator rosA. Cross-species comparison has revealed that 8.5%, 13.5% and 12.6%, respectively, of A. fumigatus, N. fischeri and A. clavatus genes are species-specific. These genes are significantly smaller in size than core genes, contain fewer exons and exhibit a subtelomeric bias. Most of them cluster together in 13 chromosomal islands, which are enriched for pseudogenes, transposons and other repetitive elements. At least 20% of A. fumigatus-specific genes appear to be functional and involved in carbohydrate and chitin catabolism, transport, detoxification, secondary metabolism and other functions that may facilitate the adaptation to heterogeneous environments such as soil or a mammalian host. Contrary to what was suggested previously, their origin cannot be attributed to horizontal gene transfer (HGT), but instead is likely to involve duplication, diversification and differential gene loss (DDL). The role of duplication in the origin of lineage-specific genes is further underlined by the discovery of genomic islands that seem to function as designated “gene dumps” and, perhaps, simultaneously, as “gene factories”. Aspergillus is an extremely diverse genus of filamentous ascomycetous fungi (molds) found ubiquitously in soil and decomposing vegetation. Being supreme opportunists, aspergilli have adapted to overcome various chemical, physical, and biological stresses found in heterogeneous environments. While most species in the genus are saprophytes, a surprising number are able to infect wounded plants and animals. Remarkably, the allergic human host also responds abnormally to the aspergilli with lung and sinus disease. The advent of immunosuppressive agents and other medical advances have created a large worldwide pool of human hosts susceptible to some Aspergillus species, including the world's most harmful mold and the causative agent of invasive aspergillosis, Aspergillus fumigatus. In this study, we have used the power of comparative genomics to gain insight into genetic mechanisms that may contribute to the metabolic versatility and pathogenicity of this important human pathogen. Comparison of the genomes of two A. fumigatus clinical isolates and two closely related, but rarely pathogenic species showed that their genomes contain several large isolate- and species-specific chromosomal islands. The metabolic capabilities encoded by these highly labile regions are likely to contribute to their rapid adaptation to heterogeneous environments such as soil or a living host.
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影响因子：
10.7
作者：
Castresana, J
通讯作者：
Castresana, J
DOI：
10.1111/j.1365-2222.1977.tb01485.x
发表时间：
1977-01-01
期刊：
CLINICAL ALLERGY
影响因子：
--
作者：
BLYTH, W;GRANT, IWB;GREENBERG, M
通讯作者：
GREENBERG, M
影响因子：
4.4
作者：
Fedorova ND;Badger JH;Robson GD;Wortman JR;Nierman WC
通讯作者：
Nierman WC
影响因子：
56.9
作者：
FLEISCHMANN, RD;ADAMS, MD;VENTER, JC
通讯作者：
VENTER, JC
影响因子：
2.9
作者：
Clemons, KV;Miller, TK;Stevens, DA
通讯作者：
Stevens, DA