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登革病毒4型的群体基因组学:对遗传结构和进化的见解

Population genomics of dengue virus serotype 4: insights into genetic structure and evolution.

作者信息

Waman Vaishali P, Kasibhatla Sunitha Manjari, Kale Mohan M, Kulkarni-Kale Urmila

机构信息

Bioinformatics Centre, Savitribai Phule Pune University (formerly University of Pune), Pune, 411007, India.

Bioinformatics Group, Centre for Development of Advanced Computing, Pune University Campus, Ganeshkhind, Pune, 411007, India.

出版信息

Arch Virol. 2016 Aug;161(8):2133-48. doi: 10.1007/s00705-016-2886-8. Epub 2016 May 12.

DOI:10.1007/s00705-016-2886-8
PMID:27169727
Abstract

The spread of dengue disease has become a global public health concern. Dengue is caused by dengue virus, which is a mosquito-borne arbovirus of the genus Flavivirus, family Flaviviridae. There are four dengue virus serotypes (1-4), each of which is known to trigger mild to severe disease. Dengue virus serotype 4 (DENV-4) has four genotypes and is increasingly being reported to be re-emerging in various parts of the world. Therefore, the population structure and factors shaping the evolution of DENV-4 strains across the world were studied using genome-based population genetic, phylogenetic and selection pressure analysis methods. The population genomics study helped to reveal the spatiotemporal structure of the DENV-4 population and its primary division into two spatially distinct clusters: American and Asian. These spatial clusters show further time-dependent subdivisions within genotypes I and II. Thus, the DENV-4 population is observed to be stratified into eight genetically distinct lineages, two of which are formed by American strains and six of which are formed by Asian strains. Episodic positive selection was observed in the structural (E) and non-structural (NS2A and NS3) genes, which appears to be responsible for diversification of Asian lineages in general and that of modern lineages of genotype I and II in particular. In summary, the global DENV-4 population is stratified into eight genetically distinct lineages, in a spatiotemporal manner with limited recombination. The significant role of adaptive evolution in causing diversification of DENV-4 lineages is discussed. The evolution of DENV-4 appears to be governed by interplay between spatiotemporal distribution, episodic positive selection and intra/inter-genotype recombination.

摘要

登革热疾病的传播已成为全球公共卫生关注的问题。登革热由登革病毒引起,该病毒是黄病毒科黄病毒属的一种蚊媒虫媒病毒。有四种登革病毒血清型(1 - 4型),已知每种血清型都可引发从轻度到重度的疾病。登革病毒4型(DENV - 4)有四种基因型,并且世界各地越来越多地报告其再度出现。因此,利用基于基因组的群体遗传学、系统发育学和选择压力分析方法,对全球DENV - 4毒株的群体结构及其进化的影响因素进行了研究。群体基因组学研究有助于揭示DENV - 4群体的时空结构及其主要划分为两个空间上不同的簇:美洲簇和亚洲簇。这些空间簇在基因型I和II内显示出进一步的时间依赖性细分。因此,观察到DENV - 4群体被分层为八个遗传上不同的谱系,其中两个由美洲毒株形成,六个由亚洲毒株形成。在结构(E)基因和非结构(NS2A和NS3)基因中观察到间歇性正选择,这似乎总体上是亚洲谱系多样化的原因,特别是基因型I和II现代谱系多样化的原因。总之,全球DENV - 4群体以时空方式分层为八个遗传上不同的谱系,重组有限。讨论了适应性进化在导致DENV - 4谱系多样化中的重要作用。DENV - 4的进化似乎受时空分布、间歇性正选择和基因型内/间重组之间相互作用的支配。

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