Patterns of nucleotide difference in overlapping and non-overlapping reading frames of papillomavirus genomes
Patterns of nucleotide difference in overlapping and non-overlapping reading frames of papillomavirus genomes
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DOI：
10.1016/j.virusres.2005.03.030
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发表时间：
2005-11-01
期刊：
影响因子：
5
通讯作者：
Hughes, MAK
中科院分区：
文献类型：
--
作者：
Hughes, AL;Hughes, MAK
在对乳头瘤病毒全基因组进行系统发育分析的基础上，选取30对亲缘关系较近的基因组，对重叠和非重叠阅读框的同义和非同义核苷酸差异模式进行了研究。与非重叠区域相比，重叠区域同义位点的同义差异比例（p(S)）普遍减少。这种p(S)的减少似乎是由于纯化选择作用于重叠的阅读框，因为它编码的氨基酸序列的功能限制。作为这种净化选择的结果，在一个阅读框中的同义替换和另一个阅读框中的非同义替换之间观察到权衡；这种模式在E2和E1阅读框之间的重叠中尤为明显，这两个阅读框编码了E2蛋白的高度保守部分。HPV16 E2蛋白的53个铰链区序列（E2和E4阅读框重叠的地方）显示E2阅读框中非同义核苷酸替换水平升高，特别是在一个被认为与免疫识别有关的区域。该区域的非同义替换不成比例地发生，从而导致E4阅读框中的同义替换。因此，E2铰链区的正向多样化选择似乎与E4重叠区的净化选择并存。(c) 2005 Elsevier B.V.版权所有
On the basis of a phylogenetic analysis of papillomavirus complete genomes, 30 pairs of closely related genomes were chosen for examination of the pattern of synonymous and non-synonymous nucleotide difference in overlapping and non-overlapping reading frames. The proportion of synonymous differences per synonymous site (p(S)) was generally reduced in overlapping regions in comparison to non-overlapping regions. This reduction in p(S) appears to result from purifying selection acting on the overlapping reading frame because of functional constraint on the amino acid sequence that it encodes. As a consequence of such purifying selection, a trade-off was observed between synonymous substitution in one reading frame and non-synonymous substitution in the other; this pattern was particularly evident in the overlap between the E2 and E1 reading frames, which encodes a highly conserved portion of the E2 protein. Fifty-three sequences of the hinge region of the HPV16 E2 protein (where the E2 and E4 reading frames overlap) showed an elevated level of non-synonymous nucleotide substitution in the E2 reading frame, particularly in a region believed to be involved in immune recognition. Non-synonymous substitutions in this region occurred disproportionately in such a way as to cause synonymous substitutions in the E4 reading frame. Thus, positive diversifying selection on the E2 hinge region appears to coexist with purifying selection on the overlapping region of E4. (c) 2005 Elsevier B.V. All rights reserved.