Determinants of substitution rates in mammalian genes: Expression pattern affects selection intensity but not mutation rate
Determinants of substitution rates in mammalian genes: Expression pattern affects selection intensity but not mutation rate
复制标题
DOI：
10.1093/oxfordjournals.molbev.a026239
复制
发表时间：
2000-01-01
影响因子：
10.7
通讯作者：
Mouchiroud, D
中科院分区：
文献类型：
--
作者：
Duret, L;Mouchiroud, D
为了确定基因表达模式是否影响哺乳动物基因的突变率和/或选择强度，我们研究了替代率和基因表达的组织分布之间的关系。为此，我们分析了 2,400 个人类/啮齿动物和 834 个小鼠/大鼠直系同源基因，并测量（使用表达序列标签数据）它们在来自三种发育状态的 19 个组织中的表达模式。我们表明，非同义位点的替换率与组织分布宽度呈强烈负相关：普遍存在的基因比组织特异性基因低几乎三倍。根据组织的不同，非同义替换率也有很大差异：脑、肌肉、视网膜和神经元特异性基因的平均替换率比淋巴细胞、肺和肝脏特异性基因低两倍。有趣的是，5' 和 3' 非翻译区 (UTR) 显示出完全相同的趋势。这些结果表明，表达模式是决定编码区和非编码区功能位点选择压力的重要因素。相反，沉默取代率不随表达模式而变化，即使在普遍表达的基因中也是如此。因此，后一个结果表明同义密码子的使用不受哺乳动物选择的限制。此外，该结果还表明，种系中表达的基因的突变率没有降低，这与基于转录DNA比非转录DNA更有效修复的事实所假设的相反。
To determine whether gene expression patterns affect mutation rates and/or selection intensity in mammalian genes, we studied the relationships between substitution rates and tissue distribution of gene expression. For this purpose, we analyzed 2,400 human/rodent and 834 mouse/rat orthologous genes, and we measured (using expressed sequence tag data) their expression patterns in 19 tissues from three development states. We show that substitution rates at nonsynonymous sites are strongly negatively correlated with tissue distribution breadth: almost threefold lower in ubiquitous than in tissue-specific genes. Nonsynonymous substitution rates also vary considerably according to the tissues: the average rate is twofold lower in brain-, muscle-, retina- and neuron-specific genes than in lymphocyte-, lung-, and liver-specific genes. Interestingly, 5' and 3' untranslated regions (UTRs) show exactly the same trend. These results demonstrate that the expression pattern is an essential factor in determining the selective pressure on functional sites in both coding and noncoding regions. Conversely, silent substitution rates do not vary with expression pattern, even in ubiquitously expressed genes. This latter result thus suggests that synonymous codon usage is not constrained by selection in mammals. Furthermore, this result also indicates that there is no reduction of mutation rates in genes expressed in the germ line, contrary to what had been hypothesized based on the fact that transcribed DNA is more efficiently repaired than nontranscribed DNA.