Genome Evolution and Innovation across the Four Major Lineages of Cryptococcus gattii.
Genome Evolution and Innovation across the Four Major Lineages of Cryptococcus gattii.
复制标题
DOI：
10.1128/mbio.00868-15
复制
发表时间：
2015-09-01
期刊：
影响因子：
6.4
通讯作者：
Cuomo CA
中科院分区：
文献类型：
--
作者：
Farrer RA;Desjardins CA;Sakthikumar S;Gujja S;Saif S;Zeng Q;Chen Y;Voelz K;Heitman J;May RC;Fisher MC;Cuomo CA
格特隐球菌是人类的一种真菌病原体，在其他健康宿主中引起肺部感染。为了表征格特隐球菌四个主要谱系（VGI、-II、-III和-IV）之间的基因组变异，我们生成、注释并比较了16个从头基因组组装，包括第一个罕见分离谱系VGIII和VGIV。通过识别跨组件的同线区域，我们发现了15个结构重排，这几乎是唯一的VGI-III-IV谱系。使用同线性来告知直系预测，我们确定了87%的核心组的C. gattii基因在所有四个谱系中以单拷贝存在。值得注意的是，737个基因是跨谱系遗传的，并且在对氧化应激、线粒体输入以及金属结合和运输的反应中被过度代表。具体而言，VGI具有被认为对隐球菌的毒力很重要的一组扩展的铁结合基因，而VGII相对于其他谱系在应激相关的热休克蛋白中具有扩展。我们还表征了每个谱系中独特缺失的基因，包括VGIV中缺失的铜转运蛋白，该转运蛋白影响肺部感染和脑膜脑炎发作期间隐球菌的存活。通过纳入另外37个分离株的群体水平数据，我们确定了一个新的横贯大陆的克隆群，我们命名为VGIIx，VGII和VGIII之间的线粒体重组，以及沿着系统发育树的多个分支的多药物转运蛋白和铁硫蛋白顺乌头酸酶沿着的正选择。我们的研究结果表明，基因扩增或收缩和积极的选择已经引入了大量的变化与整个物种的致病性机制。表型不同的病原体之间的遗传差异为这些性状的潜在机制提供了线索，并可能导致新的药物靶点和改善这些疾病的治疗方法。在本文中，我们比较了16个基因组属于四个高度分化的谱系隐球菌，导致肺部感染，否则健康的人类和其他动物。这些谱系中有一半以前没有组装和注释过它们的基因组。我们在基因组中发现了15种祖先重排和700多个基因，这些基因是一个或多个谱系所独有的，其中许多与毒力相关。此外，我们还发现了最近跨大陆传播、线粒体遗传交换和多药转运蛋白正选择的证据。我们的研究结果表明，基因扩增/收缩和积极的选择是多样化的致病机制，在这个物种复杂。
Cryptococcus gattii is a fungal pathogen of humans, causing pulmonary infections in otherwise healthy hosts. To characterize genomic variation among the four major lineages of C. gattii (VGI, -II, -III, and -IV), we generated, annotated, and compared 16 de novo genome assemblies, including the first for the rarely isolated lineages VGIII and VGIV. By identifying syntenic regions across assemblies, we found 15 structural rearrangements, which were almost exclusive to the VGI-III-IV lineages. Using synteny to inform orthology prediction, we identified a core set of 87% of C. gattii genes present as single copies in all four lineages. Remarkably, 737 genes are variably inherited across lineages and are overrepresented for response to oxidative stress, mitochondrial import, and metal binding and transport. Specifically, VGI has an expanded set of iron-binding genes thought to be important to the virulence of Cryptococcus, while VGII has expansions in the stress-related heat shock proteins relative to the other lineages. We also characterized genes uniquely absent in each lineage, including a copper transporter absent from VGIV, which influences Cryptococcus survival during pulmonary infection and the onset of meningoencephalitis. Through inclusion of population-level data for an additional 37 isolates, we identified a new transcontinental clonal group that we name VGIIx, mitochondrial recombination between VGII and VGIII, and positive selection of multidrug transporters and the iron-sulfur protein aconitase along multiple branches of the phylogenetic tree. Our results suggest that gene expansion or contraction and positive selection have introduced substantial variation with links to mechanisms of pathogenicity across this species complex. The genetic differences between phenotypically different pathogens provide clues to the underlying mechanisms of those traits and can lead to new drug targets and improved treatments for those diseases. In this paper, we compare 16 genomes belonging to four highly differentiated lineages of Cryptococcus gattii, which cause pulmonary infections in otherwise healthy humans and other animals. Half of these lineages have not had their genomes previously assembled and annotated. We identified 15 ancestral rearrangements in the genome and over 700 genes that are unique to one or more lineages, many of which are associated with virulence. In addition, we found evidence for recent transcontinental spread, mitochondrial genetic exchange, and positive selection in multidrug transporters. Our results suggest that gene expansion/contraction and positive selection are diversifying the mechanisms of pathogenicity across this species complex.