PDF(Pubmed)
Abstract：
BACKGROUND: In vertebrates, most protein-coding genes have a peak of GC-content near their 5\' transcriptional start site (TSS). This feature promotes both the efficient nuclear export and translation of mRNAs. Despite the importance of GC-content for RNA metabolism, its general features, origin, and maintenance remain mysterious. We investigate the evolutionary forces shaping GC-content at the transcriptional start site (TSS) of genes through both comparative genomic analysis of nucleotide substitution rates between different species and by examining human de novo mutations.
RESULTS: Our data suggests that GC-peaks at TSSs were present in the last common ancestor of amniotes, and likely that of vertebrates. We observe that in apes and rodents, where recombination is directed away from TSSs by PRDM9, GC-content at the 5\' end of protein-coding gene is currently undergoing mutational decay. In canids, which lack PRDM9 and perform recombination at TSSs, GC-content at the 5\' end of protein-coding is increasing. We show that these patterns extend into the 5\' end of the open reading frame, thus impacting synonymous codon position choices.
CONCLUSIONS: Our results indicate that the dynamics of this GC-peak in amniotes is largely shaped by historic patterns of recombination. Since decay of GC-content towards the mutation rate equilibrium is the default state for non-functional DNA, the observed decrease in GC-content at TSSs in apes and rodents indicates that the GC-peak is not being maintained by selection on most protein-coding genes in those species.
RESULTS: Our data suggests that GC-peaks at TSSs were present in the last common ancestor of amniotes, and likely that of vertebrates. We observe that in apes and rodents, where recombination is directed away from TSSs by PRDM9, GC-content at the 5\' end of protein-coding gene is currently undergoing mutational decay. In canids, which lack PRDM9 and perform recombination at TSSs, GC-content at the 5\' end of protein-coding is increasing. We show that these patterns extend into the 5\' end of the open reading frame, thus impacting synonymous codon position choices.
CONCLUSIONS: Our results indicate that the dynamics of this GC-peak in amniotes is largely shaped by historic patterns of recombination. Since decay of GC-content towards the mutation rate equilibrium is the default state for non-functional DNA, the observed decrease in GC-content at TSSs in apes and rodents indicates that the GC-peak is not being maintained by selection on most protein-coding genes in those species.
摘要：
背景：在脊椎动物中，大多数蛋白质编码基因在其5'转录起始位点（TSS）附近都有GC含量的峰值。该特征促进mRNA的有效核输出和翻译。尽管GC含量对RNA代谢的重要性，它的一般特点，origin,维护仍然神秘。我们通过对不同物种之间的核苷酸取代率进行比较基因组分析以及通过检查人类从头突变，研究了在基因转录起始位点（TSS）处形成GC含量的进化力。
结果：我们的数据表明，TSS的GC峰存在于羊膜的最后一个共同祖先中，可能是脊椎动物。我们观察到在类人猿和啮齿动物中，在PRDM9引导重组远离TSS的情况下，蛋白质编码基因5'末端的GC含量目前正在发生突变衰减。在犬科动物中，缺少PRDM9并在TSS上进行重组，蛋白质编码5'端的GC含量正在增加。我们证明这些模式延伸到开放阅读框架的5'末端，从而影响同义密码子的位置选择。
结论：我们的结果表明，羊膜中这种GC峰的动力学很大程度上是由重组的历史模式决定的。由于GC含量朝向突变率平衡的衰减是无功能DNA的默认状态，在猿和啮齿动物中观察到的TSS的GC含量降低表明，在这些物种中大多数蛋白质编码基因的选择不能维持GC峰。
结果：我们的数据表明，TSS的GC峰存在于羊膜的最后一个共同祖先中，可能是脊椎动物。我们观察到在类人猿和啮齿动物中，在PRDM9引导重组远离TSS的情况下，蛋白质编码基因5'末端的GC含量目前正在发生突变衰减。在犬科动物中，缺少PRDM9并在TSS上进行重组，蛋白质编码5'端的GC含量正在增加。我们证明这些模式延伸到开放阅读框架的5'末端，从而影响同义密码子的位置选择。
结论：我们的结果表明，羊膜中这种GC峰的动力学很大程度上是由重组的历史模式决定的。由于GC含量朝向突变率平衡的衰减是无功能DNA的默认状态，在猿和啮齿动物中观察到的TSS的GC含量降低表明，在这些物种中大多数蛋白质编码基因的选择不能维持GC峰。
