Mapping overlapping functional elements embedded within the protein-coding regions of RNA viruses.

Mapping overlapping functional elements embedded within the protein-coding regions of RNA viruses.
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DOI:
10.1093/nar/gku981
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发表时间:
2014-11-10
影响因子:
14.9
通讯作者:
Firth AE
Firth AE
中科院分区:
生物学2区
文献类型:
--
作者:
Firth AE

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鉴定任何病毒中完整的基因和其他功能元件对于充分了解其分子生物学和指导有效控制策略的制定至关重要。 RNA病毒具有紧凑的多功能基因组,通常包含重叠基因和嵌入蛋白质编码序列中的非编码功能元件。重叠特征通常会逃避检测,因为通过突变分析很难区分组成核苷酸的多重作用,而高通量实验技术通常无法区分功能元件和偶然特征。然而,RNA病毒进化得非常迅速,因此,即使在单一物种内,替换也会在中性或近中性位点迅速积累,为比较基因组学区分纯化选择的特征提供了巨大的潜力。然后可以有效地针对计算识别的特征进行实验分析。在这里,我们分析了蛋白质编码病毒序列的比对,以识别同义位点变异程度统计上显着降低的区域,这是重叠功能元件的特征。我们之前通过对选定病毒中的发现进行实验验证来测试了这项技术,现在我们分析了~700种RNA病毒的序列比对,以识别数百个这样的区域,其中许多区域以前没有被描述过。
Identification of the full complement of genes and other functional elements in any virus is crucial to fully understand its molecular biology and guide the development of effective control strategies. RNA viruses have compact multifunctional genomes that frequently contain overlapping genes and non-coding functional elements embedded within protein-coding sequences. Overlapping features often escape detection because it can be difficult to disentangle the multiple roles of the constituent nucleotides via mutational analyses, while high-throughput experimental techniques are often unable to distinguish functional elements from incidental features. However, RNA viruses evolve very rapidly so that, even within a single species, substitutions rapidly accumulate at neutral or near-neutral sites providing great potential for comparative genomics to distinguish the signature of purifying selection. Computationally identified features can then be efficiently targeted for experimental analysis. Here we analyze alignments of protein-coding virus sequences to identify regions where there is a statistically significant reduction in the degree of variability at synonymous sites, a characteristic signature of overlapping functional elements. Having previously tested this technique by experimental verification of discoveries in selected viruses, we now analyze sequence alignments for ∼700 RNA virus species to identify hundreds of such regions, many of which have not been previously described.
流感A病毒表达中使用的核糖体框架发生在序列UCC_UUU_CGU内,并且位于+1方向。
DOI: 10.1098/rsob.120109
发表时间: 2012-10
期刊: Open biology
影响因子: 5.8
作者:
Firth AE;Jagger BW;Wise HM;Nelson CC;Parsawar K;Wills NM;Napthine S;Taubenberger JK;Digard P;Atkins JF
通讯作者: Atkins JF
DOI: 10.1016/j.virol.2008.06.034
发表时间: 2008-09-30
期刊: VIROLOGY
影响因子: 3.7
作者:
Clyde, Karen;Barrera, Julio;Harris, Eva
通讯作者: Harris, Eva
DOI: 10.1186/1743-422x-5-108
发表时间: 2008-09-26
期刊: Virology journal
影响因子: 4.8
作者:
Firth AE;Chung BY;Fleeton MN;Atkins JF
通讯作者: Atkins JF
DOI: 10.1128/jvi.70.9.5884-5892.1996
发表时间: 1996-09-01
影响因子: 5.4
作者:
Brown, CM;DineshKumar, SP;Miller, WA
通讯作者: Miller, WA
DOI: 10.1099/vir.0.042499-0
发表时间: 2012-07
期刊: The Journal of general virology
影响因子: --
作者:
Firth AE;Brierley I
通讯作者: Brierley I