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鼻病毒的种群结构与进化。

Population structure and evolution of Rhinoviruses.

机构信息

Bioinformatics Centre, University of Pune, Pune, India.

Department of Statistics, University of Pune, Pune, India.

出版信息

PLoS One. 2014 Feb 19;9(2):e88981. doi: 10.1371/journal.pone.0088981. eCollection 2014.

Abstract

Rhinoviruses, formerly known as Human rhinoviruses, are the most common cause of air-borne upper respiratory tract infections in humans. Rhinoviruses belong to the family Picornaviridae and are divided into three species namely, Rhinovirus A, -B and -C, which are antigenically diverse. Genetic recombination is found to be one of the important causes for diversification of Rhinovirus species. Although emerging lineages within Rhinoviruses have been reported, their population structure has not been studied yet. The availability of complete genome sequences facilitates study of population structure, genetic diversity and underlying evolutionary forces, such as mutation, recombination and selection pressure. Analysis of complete genomes of Rhinoviruses using a model-based population genetics approach provided a strong evidence for existence of seven genetically distinct subpopulations. As a result of diversification, Rhinovirus A and -C populations are divided into four and two subpopulations, respectively. Genetically, the Rhinovirus B population was found to be homogeneous. Intra-species recombination was observed to be prominent in Rhinovirus A and -C species. Significant evidence of episodic positive selection was obtained for several sites within coding sequences of structural and non-structural proteins. This corroborates well with known phenotypic properties such as antigenicity of structural proteins. Episodic positive selection appears to be responsible for emergence of new lineages especially in Rhinovirus A. In summary, the Rhinovirus population is an ensemble of seven distinct lineages. In case of Rhinovirus A, intra-species recombination and episodic positive selection contribute to its further diversification. In case of Rhinovirus C, intra- and inter-species recombinations are responsible for observed diversity. Population genetics approach was further useful to analyze phylogenetic tree topologies pertaining to recombinant strains, especially when trees are derived using complete genomes. Understanding of population structure serves as a foundation for designing new vaccines and drugs as well as to explain emergence of drug resistance amongst subpopulations.

摘要

鼻病毒,以前称为人类鼻病毒,是人类空气传播上呼吸道感染最常见的原因。鼻病毒属于小核糖核酸病毒科,分为三个种,即鼻病毒 A、B 和 C,它们具有不同的抗原性。遗传重组被认为是鼻病毒种多样化的重要原因之一。虽然已经报道了鼻病毒中的新兴谱系,但尚未研究其种群结构。完整基因组序列的可用性便于研究种群结构、遗传多样性以及潜在的进化力量,如突变、重组和选择压力。使用基于模型的群体遗传学方法对鼻病毒的完整基因组进行分析,为存在七个遗传上不同的亚群提供了强有力的证据。由于多样化,鼻病毒 A 和 C 种群分别分为四个和两个亚群。遗传上,鼻病毒 B 种群是同质的。在鼻病毒 A 和 C 种中观察到种内重组很突出。在结构和非结构蛋白的编码序列中,几个位点都获得了显著的正选择证据。这与已知的表型特性(如结构蛋白的抗原性)非常吻合。间断性正选择似乎是导致新谱系出现的原因,尤其是在鼻病毒 A 中。总之,鼻病毒种群是由七个不同谱系组成的集合体。在鼻病毒 A 中,种内重组和间断性正选择有助于其进一步多样化。在鼻病毒 C 中,种内和种间重组是造成观察到的多样性的原因。群体遗传学方法还可用于分析与重组株相关的系统发育树拓扑结构,特别是在使用完整基因组生成树时。对种群结构的了解是设计新疫苗和药物的基础,也是解释亚群中出现药物耐药性的基础。

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