A test of translational selection at 'silent' sites in the human genome: base composition comparisons in alternatively spliced genes
A test of translational selection at 'silent' sites in the human genome: base composition comparisons in alternatively spliced genes
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DOI：
10.1016/s0378-1119(00)00482-0
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发表时间：
2000-12-30
期刊：
影响因子：
3.5
通讯作者：
Akashi, H
中科院分区：
文献类型：
--
作者：
Iida, K;Akashi, H
自然选择似乎区分同义密码子，以提高翻译效率，在广泛的原核生物和真核生物。密码子偏好性与这些物种的基因表达水平密切相关。此外，沉默DNA趋异中的基因间变异与密码子偏好性呈负相关。然而，在哺乳动物中，基因间的比较是复杂的独特的核苷酸含量的偏见（isochore）在整个基因组。在这项研究中，我们试图通过分析人类和果蝇中选择性剪接基因的DNA序列来确定翻译选择。在选择性剪接基因的密码子中，组成型表达外显子中的密码子比选择性剪接外显子中的密码子更常被翻译。因此，翻译选择应该更强烈地偏向密码子的使用，并减少沉默的分歧组成比替代外显子。通过控制影响碱基组成进化的区域力量，这种基因内比较使得有可能检测哺乳动物同义位点的密码子选择。我们发现，GC结束密码子更丰富的组成比选择性剪接外显子在果蝇和人类。然而，与我们的预期相反，哺乳动物物种之间的沉默DNA分歧是组成型高于替代外显子。(C)2000 Elsevier Science B.V.保留所有权利。
Natural selection appears to discriminate among synonymous codons to enhance translational efficiency in a wide range of prokaryotes and eukaryotes. Codon bias is strongly related to gene expression levels in these species. In addition, between-gene variation in silent DNA divergence is inversely correlated with codon bias. However, in mammals, between-gene comparisons are complicated by distinctive nucleotide-content bias (isochores) throughout the genome. In this study, we attempted to identify translational selection by analyzing the DNA sequences of alternatively spliced genes in humans and in Drosophila melanogaster. Among codons in an alternatively spliced gene, those in constitutively expressed exons are translated more often than those in alternatively spliced exons. Thus, translational selection should act more strongly to bias codon usage and reduce silent divergence in constitutive than in alternative exons. By controlling for regional forces affecting base-composition evolution, this within-gene comparison makes it possible to detect codon selection at synonymous sites in mammals. We found that GC-ending codons are more abundant in constitutive than alternatively spliced exons in both Drosophila and humans. Contrary to our expectation, however, silent DNA divergence between mammalian species is higher in constitutive than in alternative exons. (C) 2000 Elsevier Science B.V. All rights reserved.