Liang Han, Landweber Laura F
Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Genome Res. 2006 Feb;16(2):190-6. doi: 10.1101/gr.4246506. Epub 2005 Dec 19.
Alternative splicing is a major mechanism for gene product regulation in many multicellular organisms. By using different exon combinations, some coding regions can encode amino acids in multiple reading frames in different transcripts. Here we performed a systematic search through a set of high-quality human transcripts and show that approximately 7% of alternatively spliced genes contain dual (multiple) coding regions. By using a conservative criterion, we found that in these regions most secondary reading frames evolved recently in mammals, and a significant proportion of them may be specific to primates. Based on the presence of in-frame stop codons in orthologous sequences in other animals, we further classified ancestral and derived reading frames in these regions. Our results indicated that ancestral reading frames are usually under stronger selection than are derived reading frames. Ancestral reading frames mainly influence the coding properties of these dual coding regions. Compared with coding regions of the whole genome, ancestral reading frames largely maintain similar nucleotide composition at each codon position and amino acid usage, while derived reading frames are significantly different. Our results also indicated that prior to acquisition of a new reading frame, the suppression of in-frame stop codons in the ancestral state is mainly achieved by one-step transition substitutions at the first or second codon position. Finally, the selective forces imposed on these dual coding regions will also be discussed.
可变剪接是许多多细胞生物中基因产物调控的主要机制。通过使用不同的外显子组合，一些编码区域可以在不同转录本的多个阅读框中编码氨基酸。在这里，我们通过一组高质量的人类转录本进行了系统搜索，结果表明约7%的可变剪接基因包含双重（多个）编码区域。通过使用保守标准，我们发现，在这些区域中，大多数二级阅读框是最近在哺乳动物中进化而来的，并且其中很大一部分可能是灵长类特有的。基于其他动物直系同源序列中框内终止密码子的存在，我们进一步对这些区域中的祖先阅读框和衍生阅读框进行了分类。我们的结果表明，祖先阅读框通常比衍生阅读框受到更强的选择。祖先阅读框主要影响这些双重编码区域的编码特性。与整个基因组的编码区域相比，祖先阅读框在每个密码子位置的核苷酸组成和氨基酸使用情况上基本保持相似，而衍生阅读框则有显著差异。我们的结果还表明，在获得新的阅读框之前，祖先状态下框内终止密码子的抑制主要通过在第一个或第二个密码子位置的一步转换替换来实现。最后，我们还将讨论施加在这些双重编码区域上的选择力。
