Selective and mutational patterns associated with gene expression in humans: Influences on synonymous composition and intron presence
Selective and mutational patterns associated with gene expression in humans: Influences on synonymous composition and intron presence
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DOI：
10.1534/genetics.104.026351
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发表时间：
2004-07-01
期刊：
影响因子：
3.3
通讯作者：
Comeron, JM
中科院分区：
文献类型：
--
作者：
Comeron, JM
我们报道了一项关于基因表达对人类蛋白质编码基因中同义密码子、氨基酸组成、内含子存在和大小影响的综合研究结果。首先，除了等位基因的强烈作用外，我们还检测到了转录相关突变偏向(TAMB)对基因组成的影响。在不同组织中表达的基因表现出不同程度的TAMB，其中在睾丸中表达的基因影响最大。其次，对没有TAMB证据的组织的研究揭示了一组一致的最佳同义密码子，这些密码子在高表达的基因中受到青睐。这一结果揭示了自然选择对同义成分的影响，以提高人类谱系中翻译的效率。第三，蛋白质的总氨基酸组成与tRNA丰度非常相似，但差异表达基因的氨基酸组成没有差异。第四，表达与CDS长度呈负相关。值得注意的是，这只在带有内含子的基因中观察到，这表明人类这种关系的原因不能只与氨基酸生物合成的成本有关。第五，我们表明，广泛和高表达的基因有更多的内含子，尽管更短。在高表达基因中有更多内含子的选择优势可能被转录成本的控制和适当剪接的最小外显子大小所抵消。
We report the results of a comprehensive study of the influence of gene expression on synonymous codons, amino acid composition, and intron presence and size in human protein-coding genes. First, in addition to a strong effect of isochores, we have detected the influence of transcription-associated mutational biases (TAMB) on gene composition. Genes expressed in different tissues show diverse degrees of TAMB, with genes expressed in testis showing the greatest influence. Second, the study of tissues with no evidence of TAMB reveals a consistent set of optimal synonymous codons favored in highly expressed genes. This result exposes the consequences of natural selection on synonymous composition to increase efficiency of translation in the human lineage. Third, overall amino acid composition of proteins closely resembles tRNA abundance but there is no difference in amino acid composition in differentially expressed genes. Fourth, there is a negative relationship between expression and CDS length. Significantly, this is observed only among genes with introns, suggesting that the cause for this relationship in humans cannot be associated only with costs of amino acid biosynthesis. Fifth, we show that broadly and highly expressed genes have more, although shorter, introns. The selective advantage for having more introns in highly expressed genes is likely counterbalanced by containment of transcriptional costs and a minimum exon size for proper splicing.