The genomic features that affect the lengths of 5' untranslated regions in multicellular eukaryotes.
The genomic features that affect the lengths of 5' untranslated regions in multicellular eukaryotes.
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DOI：
10.1186/1471-2105-12-s9-s3
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发表时间：
2011-10-05
影响因子：
3
通讯作者：
Chen FC
中科院分区：
文献类型：
--
作者：
Chen CH;Lin HY;Pan CL;Chen FC
多细胞真核生物的5'UTR长度被认为是随机变化的，上游启动密码子（uAUGs）是抑制5'UTR延伸的主要约束。然而，这种随机模型不能完全解释5'UTR长度的变化。我们假设基因组特征组合的选择压力对5'UTR进化也很重要。对这些特征的无知可能限制了随机模型的解释能力。此外，脊椎动物和无脊椎动物之间不同的选择约束可能导致5'UTR长度决定因素的差异，这一点尚未得到系统的分析。在这里，我们使用多元线性回归模型来描述5'UTR长度与一系列基因组特征（G+C含量，uAUGs的观察与预期（OE）比率，上游停止密码子（ustop），甲基化相关的CG/UG二核苷酸，以及mrna不稳定的UU/UA二核苷酸）的组合之间的相关性，这些特征包括6种脊椎动物（人类，小鼠，大鼠，鸡，非洲爪蛙和马马鱼）和4种无脊椎动物（果蝇，蚊子，海鞘和线虫）。并对各特征对5'UTR长度变化的相对贡献进行了评价。我们发现，14%~33%的5'UTR长度变异可以用所分析的基因组特征的线性组合来解释。最重要的基因组特征是ustop的OE比率和G+C含量。ustop惊人的大权重突出了上游开放阅读帧（包括uaug和ustop）选择的重要性，而不是uaug本身。此外，G+C含量对大多数无脊椎动物来说是最重要的决定因素，但对脊椎动物来说，它的影响仅次于ustop。我们还发现，较短的5 ' utr更受随机过程的影响，而较长的5 ' utr更受基因组特征选择压力的影响。我们的研究结果表明，上游开放阅读帧可能是选择的真正目标，而不是uaug。我们还表明，5 ' utr基因组特征的选择性约束在脊椎动物和无脊椎动物之间，以及在更长和更短的5 ' utr之间存在差异。需要一个更全面的模型来考虑这些发现，以更好地解释5'UTR长度的进化。
The lengths of 5’UTRs of multicellular eukaryotes have been suggested to be subject to stochastic changes, with upstream start codons (uAUGs) as the major constraint to suppress 5’UTR elongation. However, this stochastic model cannot fully explain the variations in 5’UTR length. We hypothesize that the selection pressure on a combination of genomic features is also important for 5’UTR evolution. The ignorance of these features may have limited the explanatory power of the stochastic model. Furthermore, different selective constraints between vertebrates and invertebrates may lead to differences in the determinants of 5’UTR length, which have not been systematically analyzed. Here we use a multiple linear regression model to delineate the correlation between 5’UTR length and the combination of a series of genomic features (G+C content, observed-to-expected (OE) ratios of uAUGs, upstream stop codons (uSTOPs), methylation-related CG/UG dinucleotides, and mRNA-destabilizing UU/UA dinucleotides) in six vertebrates (human, mouse, rat, chicken, African clawed frog, and zebrafish) and four invertebrates (fruit fly, mosquito, sea squirt, and nematode). The relative contributions of each feature to the variation of 5’UTR length were also evaluated. We found that 14%~33% of the 5’UTR length variations can be explained by a linear combination of the analyzed genomic features. The most important genomic features are the OE ratios of uSTOPs and G+C content. The surprisingly large weightings of uSTOPs highlight the importance of selection on upstream open reading frames (which include both uAUGs and uSTOPs), rather than on uAUGs per se. Furthermore, G+C content is the most important determinants for most invertebrates, but for vertebrates its effect is second to uSTOPs. We also found that shorter 5’UTRs are affected more by the stochastic process, whereas longer 5’UTRs are affected more by selection pressure on genomic features. Our results suggest that upstream open reading frames may be the real target of selection, rather than uAUGs. We also show that the selective constraints on genomic features of 5’UTRs differ between vertebrates and invertebrates, and between longer and shorter 5’UTRs. A more comprehensive model that takes these findings into consideration is needed to better explain 5’UTR length evolution.