Canalization of the evolutionary trajectory of the human influenza virus.

Canalization of the evolutionary trajectory of the human influenza virus.
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DOI:
10.1186/1741-7007-10-38
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发表时间:
2012-04-30
期刊:
影响因子:
5.4
通讯作者:
Pascual M
Pascual M
中科院分区:
生物学2区
文献类型:
--
作者:
Bedford T;Rambaut A;Pascual M

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自1968年出现以来,甲型H3N2流感在基因型和抗原表型方面发生了广泛的演变。然而,尽管有强大的压力,进化远离人类免疫和多样化的抗原表型,H3N2流感显示矛盾有限的遗传和抗原多样性存在于任何一个时间。在这里,我们提出了一个简单的流感病毒抗原进化模型,解释了这种明显的差异。在该模型中,抗原表型由N维向量表示,并且病毒突变在该连续欧几里得空间内扰动表型。我们在一个大规模的基于个体的模拟中实现了这个模型,在这样做的过程中,我们发现模型行为和观察到的流感动态之间有着显着的对应关系。这种模式显示出快速的进化,但低常设多样性,同时占流行病学,遗传,抗原和地理模式显示的病毒。我们发现,从现有的人类免疫力的进化,在流感病毒的快速人口更替的结果,这种人口更替主要发生沿着一个单一的抗原轴。选择性动力学诱导了一个渠道化的进化轨迹,其中流感种群的进化命运是惊人的可重复性。在该模型中,流感人口显示出1至2年的可重复性时间尺度,这表明在理论上可以预测进化动力学的窗口。
Since its emergence in 1968, influenza A (H3N2) has evolved extensively in genotype and antigenic phenotype. However, despite strong pressure to evolve away from human immunity and to diversify in antigenic phenotype, H3N2 influenza shows paradoxically limited genetic and antigenic diversity present at any one time. Here, we propose a simple model of antigenic evolution in the influenza virus that accounts for this apparent discrepancy. In this model, antigenic phenotype is represented by a N-dimensional vector, and virus mutations perturb phenotype within this continuous Euclidean space. We implement this model in a large-scale individual-based simulation, and in doing so, we find a remarkable correspondence between model behavior and observed influenza dynamics. This model displays rapid evolution but low standing diversity and simultaneously accounts for the epidemiological, genetic, antigenic, and geographical patterns displayed by the virus. We find that evolution away from existing human immunity results in rapid population turnover in the influenza virus and that this population turnover occurs primarily along a single antigenic axis. Selective dynamics induce a canalized evolutionary trajectory, in which the evolutionary fate of the influenza population is surprisingly repeatable. In the model, the influenza population shows a 1- to 2-year timescale of repeatability, suggesting a window in which evolutionary dynamics could be, in theory, predictable.
DOI: 10.1084/jem.78.5.407
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