Civetta Alberto, Ostapchuk David Cecil Murphy, Nwali Basil
Department of Biology, University of Winnipeg, Winnipeg, Manitoba R3B 2G3, Canada
Department of Physics, University of Winnipeg, Winnipeg, Manitoba, Canada.
Genome Biol Evol. 2016 Apr 8;8(4):986-93. doi: 10.1093/gbe/evw061.
In recent years a number of studies have brought attention to the role of positive selection during the evolution of antigenic escape by influenza strains. Particularly, the identification of positively selected sites within antigenic domains of viral surface proteins has been used to suggest that the evolution of viral-host receptor binding specificity is driven by selection. Here we show that, following the 1918 outbreak, the antigenic sites of the hemagglutinin (HA) viral surface protein and the stalk region of neuraminidase became substitution hotspots. The hotspots show similar patterns of nucleotide substitution bias at synonymous and nonsynonymous sites. Such bias imposes directionality in amino acid replacements that can influence signals of selection at antigenic sites. Our results suggest that the high accumulation of substitutions within the antigenic sites of HA can explain not only cases of antigenic escape by antigenic drift but also lead to occasional episodes of viral extinction.
近年来，多项研究已将人们的注意力引向正向选择在流感病毒株抗原逃逸进化过程中的作用。特别是，通过鉴定病毒表面蛋白抗原结构域内的正向选择位点，有人提出病毒-宿主受体结合特异性的进化是由选择驱动的。在此我们表明，1918年流感大流行之后，血凝素（HA）病毒表面蛋白的抗原位点以及神经氨酸酶的柄部区域成为了替换热点。这些热点在同义位点和非同义位点显示出相似的核苷酸替换偏向模式。这种偏向在氨基酸替换中施加了方向性，进而可能影响抗原位点处的选择信号。我们的研究结果表明，HA抗原位点内替换的高度积累不仅可以解释抗原漂移导致的抗原逃逸情况，还可能偶尔导致病毒灭绝事件。
