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The Evolving Profile of the Signature Amino Acid Residues in HIV-1 Subtype C Tat

机译:HIV-1亚型C Tat中标志性氨基酸残基的演变概况

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摘要

Using several HIV-1 tat exon 1 amino acid sequences available from public databases and additional sequences derived from a southern Indian clinical cohort, we compared the profile of the signature amino acid residues (SAR) between two different time periods, 1986-2004 and 2005-2014. The analysis identified eight positions as signature residues in subtype C Tat and demonstrated a changing pattern at four of these positions between the two periods. At three locations (histidine 29, serine 57, and proline 60), there appears to be a nonuniform negative selection against the SAR. The negative selection appears to be severe, especially against histidine 29 (p<.0001) and moderate against proline 60 (p<.0001). The negative selection against serine 57 is statistically insignificant and appears to have begun recently. At position 63, the frequency of signature residue glutamic acid increased over the past decade, although the difference was not significant. Importantly, at the three locations where the negative selection is in progress, the substitute amino acids are the generic residues present in most of the other HIV-1 subtypes. Our data demonstrate that viral evolution can subject specific amino acid residues to subtle and progressive selection pressures without affecting the prevalence of other amino acid residues.
机译:使用可从公共数据库获得的几种HIV-1 tat外显子1氨基酸序列以及从印度南部临床队列获得的其他序列,我们比较了两个不同时间段(1986-2004年和2005年)之间的特征性氨基酸残基(SAR)的概况-2014。分析确定了八个位置作为亚型C Tat中的标志残基,并显示了两个时期之间四个位置的变化模式。在三个位置(组氨酸29,丝氨酸57和脯氨酸60),似乎对SAR的阴性选择不一致。负选择似乎很严重,尤其是对组氨酸29(p <.0001)和对脯氨酸60(p <.0001)的中等。对丝氨酸57的阴性选择在统计上是微不足道的,并且似乎是最近才开始的。尽管位置差异不大,但在过去的十年中,位置63的特征性谷氨酸残基的频率增加了。重要的是,在进行负选择的三个位置上,替代氨基酸是大多数其他HIV-1亚型中存在的通用残基。我们的数据表明,病毒进化可以使特定的氨基酸残基经受微妙和逐步的选择压力,而不会影响其他氨基酸残基的流行。

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