Orphan Genes Shared by Pathogenic Genomes Are More Associated with Bacterial Pathogenicity
Orphan Genes Shared by Pathogenic Genomes Are More Associated with Bacterial Pathogenicity
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DOI：
10.1128/msystems.00290-18
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发表时间：
2019-01-01
期刊：
影响因子：
6.4
通讯作者：
Yin, Yanbin
中科院分区：
文献类型：
--
作者：
Entwistle, Sarah;Li, Xueqiong;Yin, Yanbin
孤儿基因（也称为ORFans[即孤儿开放阅读框]）是使生物体能够适应其特定生存环境的新基因。本研究的重点是比较同一属病原菌(P)和非病原菌（NP）之间的ORFans。利用泛基因组的思想，我们在9个细菌属（505个基因组）中鉴定出130,169个ORFans，并将这些ORFans分为4组：(i) SS-ORFans (P)，仅在单个致病基因组中发现；（ii） SS-ORFans (NP)，仅在单个非致病性基因组中发现；（iii）存在于多个致病基因组中的PS-ORFans (P)；（iv）在多个非致病性基因组中发现的NS-ORFans （NP）。在同一属中，病原体并不总是比非病原体具有更多的基因、更多的orfan或更多的致病性相关基因（PRGs），包括噬菌体、致病性岛（PAIs）、毒力因子（VFs）和水平基因转移（hgt）。有趣的是，在9个属的病原体中，PS-ORFans的百分比始终高于SS-ORFans，而在非病原体中则并非如此。同样，在9个属的病原菌中，PS-ORFans与4种PRGs匹配的比例也始终高于SS-ORFans，但在非病原菌中并非如此。所有这些发现都表明PS-ORFans对细菌致病性的重要性更大。最近对许多细菌物种的泛基因组分析表明，单个物种的每个基因组可能具有其基因内容的很大一部分是独特的或由极少数基因组（即ORFans）共享的。我们选择了9个细菌属，每个属至少包含5个致病性和5个非致病性基因组，比较它们的orfan与致病性相关基因的关系。已知这些属的病原体可引起许多常见和破坏性的人类疾病，如肺炎、白喉、类鼻疽和结核病。因此，它们值得进行深入的系统微生物学研究，包括病原体与非病原体之间的ORFans比较研究。我们提供的直接证据表明，更多的病原体共享的orfan与致病性相关基因的相关性更强，因此更有可能成为开发新的细菌感染性疾病诊断标志物或治疗药物的重要靶点。
Orphan genes (also known as ORFans [i.e., orphan open reading frames]) are new genes that enable an organism to adapt to its specific living environment. Our focus in this study is to compare ORFans between pathogens (P) and nonpathogens (NP) of the same genus. Using the pangenome idea, we have identified 130,169 ORFans in nine bacterial genera (505 genomes) and classified these ORFans into four groups: (i) SS-ORFans (P), which are only found in a single pathogenic genome; (ii) SS-ORFans (NP), which are only found in a single nonpathogenic genome; (iii) PS-ORFans (P), which are found in multiple pathogenic genomes; and (iv) NS-ORFans (NP), which are found in multiple nonpathogenic genomes. Within the same genus, pathogens do not always have more genes, more ORFans, or more pathogenicity-related genes (PRGs)-including prophages, pathogenicity islands (PAIs), virulence factors (VFs), and horizontal gene transfers (HGTs)-than nonpathogens. Interestingly, in pathogens of the nine genera, the percentages of PS-ORFans are consistently higher than those of SS-ORFans, which is not true in nonpathogens. Similarly, in pathogens of the nine genera, the percentages of PS-ORFans matching the four types of PRGs are also always higher than those of SS-ORFans, but this is not true in nonpathogens. All of these findings suggest the greater importance of PS-ORFans for bacterial pathogenicity.IMPORTANCE Recent pangenome analyses of numerous bacterial species have suggested that each genome of a single species may have a significant fraction of its gene content unique or shared by a very few genomes (i.e., ORFans). We selected nine bacterial genera, each containing at least five pathogenic and five nonpathogenic genomes, to compare their ORFans in relation to pathogenicity-related genes. Pathogens in these genera are known to cause a number of common and devastating human diseases such as pneumonia, diphtheria, melioidosis, and tuberculosis. Thus, they are worthy of in-depth systems microbiology investigations, including the comparative study of ORFans between pathogens and nonpathogens. We provide direct evidence to suggest that ORFans shared by more pathogens are more associated with pathogenicity-related genes and thus are more important targets for development of new diagnostic markers or therapeutic drugs for bacterial infectious diseases.