Department of Life Sciences, University of Parma, I-43124 Parma, Italy.
PLoS Comput Biol. 2013;9(8):e1003162. doi: 10.1371/journal.pcbi.1003162. Epub 2013 Aug 15.
A well-known mechanism through which new protein-coding genes originate is by modification of pre-existing genes, e.g. by duplication or horizontal transfer. In contrast, many viruses generate protein-coding genes de novo, via the overprinting of a new reading frame onto an existing ("ancestral") frame. This mechanism is thought to play an important role in viral pathogenicity, but has been poorly explored, perhaps because identifying the de novo frames is very challenging. Therefore, a new approach to detect them was needed. We assembled a reference set of overlapping genes for which we could reliably determine the ancestral frames, and found that their codon usage was significantly closer to that of the rest of the viral genome than the codon usage of de novo frames. Based on this observation, we designed a method that allowed the identification of de novo frames based on their codon usage with a very good specificity, but intermediate sensitivity. Using our method, we predicted that the Rex gene of deltaretroviruses has originated de novo by overprinting the Tax gene. Intriguingly, several genes in the same genomic region have also originated de novo and encode proteins that regulate the functions of Tax. Such "gene nurseries" may be common in viral genomes. Finally, our results confirm that the genomic GC content is not the only determinant of codon usage in viruses and suggest that a constraint linked to translation must influence codon usage.
一种众所周知的新蛋白质编码基因起源的机制是通过修饰预先存在的基因，例如通过复制或水平转移。相比之下，许多病毒通过在现有（“祖先”）框架上重叠新的阅读框来从头生成蛋白质编码基因。这种机制被认为在病毒的致病性中起着重要作用，但尚未得到充分探索，也许是因为识别从头开始的框架非常具有挑战性。因此，需要一种新的方法来检测它们。我们组装了一组重叠基因的参考集，我们可以可靠地确定其祖先框架，并发现它们的密码子使用与病毒基因组其余部分的密码子使用非常接近，而不是与从头开始的框架的密码子使用接近。基于这一观察结果，我们设计了一种方法，该方法可以根据其密码子使用来识别从头开始的框架，具有非常好的特异性，但敏感性中等。使用我们的方法，我们预测德尔塔逆转录病毒的 Rex 基因是通过重叠 Tax 基因从头开始产生的。有趣的是，同一基因组区域的几个基因也从头开始起源，并编码调节 Tax 功能的蛋白质。这种“基因苗圃”在病毒基因组中可能很常见。最后，我们的结果证实了基因组 GC 含量并不是病毒中密码子使用的唯一决定因素，并表明与翻译相关的约束因素必须影响密码子使用。
