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感染性病原体群体中的基因变异模式。

Patterns of genetic variation in populations of infectious agents.

作者信息

Gordo Isabel, Campos Paulo R A

机构信息

Instituto Gulbenkian de Ciência, Oeiras, Portugal.

出版信息

BMC Evol Biol. 2007 Jul 13;7:116. doi: 10.1186/1471-2148-7-116.

Abstract

BACKGROUND

The analysis of genetic variation in populations of infectious agents may help us understand their epidemiology and evolution. Here we study a model for assessing the levels and patterns of genetic diversity in populations of infectious agents. The population is structured into many small subpopulations, which correspond to their hosts, that are connected according to a specific type of contact network. We considered different types of networks, including fully connected networks and scale free networks, which have been considered as a model that captures some properties of real contact networks. Infectious agents transmit between hosts, through migration, where they grow and mutate until elimination by the host immune system.

RESULTS

We show how our model is closely related to the classical SIS model in epidemiology and find that: depending on the relation between the rate at which infectious agents are eliminated by the immune system and the within host effective population size, genetic diversity increases with R0 or peaks at intermediate R0 levels; patterns of genetic diversity in this model are in general similar to those expected under the standard neutral model, but in a scale free network and for low values of R0 a distortion in the neutral mutation frequency spectrum can be observed; highly connected hosts (hubs in the network) show patterns of diversity different from poorly connected individuals, namely higher levels of genetic variation, lower levels of genetic differentiation and larger values of Tajima's D.

CONCLUSION

We have found that levels of genetic variability in the population of infectious agents can be predicted by simple analytical approximations, and exhibit two distinct scenarios which are met according to the relation between the rate of drift and the rate at which infectious agents are eliminated. In one scenario the diversity is an increasing function of the level of transmission and in a second scenario it is peaked around intermediate levels of transmission. This is independent of the type of host contact structure. Furthermore for low values of R0, very heterogeneous host contact structures lead to lower levels of diversity.

摘要

背景

分析感染性病原体群体中的基因变异,有助于我们了解其流行病学特征和进化过程。在此,我们研究一种用于评估感染性病原体群体中基因多样性水平和模式的模型。该群体被构建为许多小型亚群体,这些亚群体对应于它们的宿主,并根据特定类型的接触网络相互连接。我们考虑了不同类型的网络,包括完全连接网络和无标度网络,这些网络被视为能够捕捉真实接触网络某些特性的模型。感染性病原体通过迁移在宿主之间传播,在宿主中生长和变异,直至被宿主免疫系统清除。

结果

我们展示了我们的模型与流行病学中的经典SIS模型如何密切相关,并发现:根据免疫系统清除感染性病原体的速率与宿主内有效群体大小之间的关系,基因多样性随R0增加或在中等R0水平达到峰值;该模型中的基因多样性模式总体上与标准中性模型下预期的模式相似,但在无标度网络中且R0值较低时,可观察到中性突变频率谱的扭曲;高度连接的宿主(网络中的枢纽)表现出与连接性差的个体不同的多样性模式,即更高的遗传变异水平、更低的遗传分化水平和更大的 Tajima's D 值。

结论

我们发现,感染性病原体群体中的基因变异水平可以通过简单的解析近似来预测,并呈现出两种不同的情况,这取决于漂变速率与感染性病原体被清除的速率之间的关系。在一种情况下,多样性是传播水平的递增函数,而在另一种情况下,它在中等传播水平附近达到峰值。这与宿主接触结构的类型无关。此外,对于较低的R0值,非常异质的宿主接触结构会导致更低的多样性水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adeb/1949404/60fc68282dc6/1471-2148-7-116-1.jpg

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