Genetic code redundancy and its influence on the encoded polypeptides.

Genetic code redundancy and its influence on the encoded polypeptides.
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DOI:
10.5936/csbj.201204006
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发表时间:
2012
影响因子:
6
通讯作者:
Barral JM
Barral JM
中科院分区:
生物学2区
文献类型:
--
作者:
Spencer PS;Barral JM

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遗传密码被认为是冗余的,因为相同的氨基酸残基可以由多个所谓的同义密码子编码。如果同义密码子的所有特性完全相等,人们会预期它们将沿着蛋白质编码序列均匀分布沿着。然而,过去三十年的许多研究表明,它们的分布并不完全随机。据推测,核糖体翻译某些密码子可能比其他密码子更快,因此它们的非随机分布决定了核糖体沿着mRNA的特定片段沿着移动的速度。蛋白质合成速率的这种片段变异性背后的原因,以及因此多肽从核糖体中出现的原因,已经通过理论和实验方法进行了探索。对特定密码子翻译的相对速率及其对新生链的影响的预测尚未得出明确的结论。这可能是由于,至少部分是由于密码子分类为“快”或“慢”的基础的变化,以及所分析的基因和蛋白质的数量和类型的变化。最近的方法学进展允许在整个转录组中对核糖体驻留时间进行核苷酸分辨率研究,这证实了核糖体沿着mRNA的非均匀运动,并揭示了速率控制的实际决定因素。此外,已经开始出现系统地检查核糖体运动变化的影响和新出现的多肽链的命运的实验。
The genetic code is said to be redundant in that the same amino acid residue can be encoded by multiple, so-called synonymous, codons. If all properties of synonymous codons were entirely equivalent, one would expect that they would be equally distributed along protein coding sequences. However, many studies over the last three decades have demonstrated that their distribution is not entirely random. It has been postulated that certain codons may be translated by the ribosome faster than others and thus their non-random distribution dictates how fast the ribosome moves along particular segments of the mRNA. The reasons behind such segmental variability in the rates of protein synthesis, and thus polypeptide emergence from the ribosome, have been explored by theoretical and experimental approaches. Predictions of the relative rates at which particular codons are translated and their impact on the nascent chain have not arrived at unequivocal conclusions. This is probably due, at least in part, to variation in the basis for classification of codons as “fast” or “slow”, as well as variability in the number and types of genes and proteins analyzed. Recent methodological advances have allowed nucleotide-resolution studies of ribosome residency times in entire transcriptomes, which confirm the non-uniform movement of ribosomes along mRNAs and shed light on the actual determinants of rate control. Moreover, experiments have begun to emerge that systematically examine the influence of variations in ribosomal movement and the fate of the emerging polypeptide chain.