Codon usage bias and A+T content variation in human papillomavirus genomes

Codon usage bias and A+T content variation in human papillomavirus genomes
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DOI:
10.1016/j.virusres.2003.08.019
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发表时间:
2003-12-01
期刊:
影响因子:
5
通讯作者:
Frazer, IH
Frazer, IH
中科院分区:
医学3区
文献类型:
--
作者:
Zhao, KN;Liu, WJ;Frazer, IH

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我们分析了来自三个不同系统发育组的多达79种人乳头瘤病毒(HPV)基因型的8个开放阅读框架(ORF)的密码子使用偏倚。所有8个HPV基因型的ORF显示出强烈的密码子使用偏好,其中简并编码的氨基酸,对18个密码子,主要与T在第3位。对于所有18个简并编码的氨基酸,人类和动物PV ORF之间的密码子偏好与哺乳动物基因之间的平均值显著不同。在所有HPV类型中,L2 ORF显示出最高的密码子使用偏倚(73.2 +/- 1.6%),E4 ORF最低(51.1 +/- 0.5%),反映了密码子第3位A + T含量的相似偏倚(L2:76.1 +/- 4.2%; E4:58.6 +/- 4.5%)。E4 ORF是HPV ORF中唯一富含G + C的ORF,而其他ORF则富含A + T。在E2、E6、L1和L2 ORF中,密码子使用偏好性与第3位密码子的A + T含量呈正相关,而在E4 ORF中与第3位密码子的A + T含量呈负相关。人类和非人类PV基因型中优选密码子使用的一般保守性,无论它们是否来源于相同的超群,连同观察到的HPV ORF和它们感染的细胞的基因的优选密码子使用之间的差异,表明特定的密码子使用偏好和A + T含量变化可能以某种方式增加哺乳动物上皮细胞中HPV的复制适合度,对HPV感染的基因治疗具有实际意义。(C)2003 Elsevier B. V.保留所有权利。
We analyzed the codon usage bias of eight open reading frames (ORFs) across up to 79 human papillomavirus (HPV) genotypes from three distinct phylogenetic groups. All eight ORFs across HPV genotypes show a strong codon usage bias, amongst degenerately encoded amino acids, toward 18 codons mainly with T at the 3rd position. For all 18 degenerately encoded amino acids, codon preferences amongst human and animal PV ORFs are significantly different from those averaged across mammalian genes. Across the HPV types, the L2 ORFs show the highest codon usage bias (73.2 +/- 1.6% and the E4 ORFs the lowest (51.1 +/- 0.5%), reflecting as similar bias in codon 3rd position A + T content (L2: 76.1 +/- 4.2%; E4: 58.6 +/- 4.5%). The E4 ORF, uniquely amongst the HPV ORFs, is G + C rich, while the other ORFs are A + T rich. Codon usage bias correlates positively with A + T content at the codon 3rd position in the E2, E6, L1 and L2 ORFs, but negatively in the E4 ORFs. A general conservation of preferred codon usage across human and non-human PV genotypes whether they originate from a same supergroup or not, together with observed difference between the preferred codon usage for HPV ORFs and for genes of the cells they infect, suggests that specific codon usage bias and A + T content variation may somehow increase the replicational fitness of HPVs in mammalian epithelial cells, and have practical implications for gene therapy of HPV infection. (C) 2003 Elsevier B.V. All rights reserved.