Osada Naoki, Hirata Makoto, Tanuma Reiko, Kusuda Jun, Hida Munetomo, Suzuki Yutaka, Sugano Sumio, Gojobori Takashi, Shen C-K James, Wu Chung-I, Hashimoto Katsuyuki
Division of Genetic Resources, National Institute of Infectious Diseases, Tokyo, Japan.
Mol Biol Evol. 2005 Oct;22(10):1976-82. doi: 10.1093/molbev/msi187. Epub 2005 Jun 8.
The substitution rate and structural divergence in the 5'-untranslated region (UTR) were investigated by using human and cynomolgus monkey cDNA sequences. Due to the weaker functional constraint in the UTR than in the coding sequence, the divergence between humans and macaques would provide a good estimate of the nucleotide substitution rate and structural divergence in the 5'UTR. We found that the substitution rate in the 5'UTR (K5UTR) averaged approximately 10%-20% lower than the synonymous substitution rate (Ks). However, both the K5UTR and nonsynonymous substitution rate (Ka) were significantly higher in the testicular cDNAs than in the brain cDNAs, whereas the Ks did not differ. Further, an in silico analysis revealed that 27% (169/622) of macaque testicular cDNAs had an altered exon-intron structure in the 5'UTR compared with the human cDNAs. The fraction of cDNAs with an exon alteration was significantly higher in the testicular cDNAs than in the brain cDNAs. We confirmed by using reverse transcriptase-polymerase chain reaction that about one-third (6/16) of in silico "macaque-specific" exons in the 5'UTR were actually macaque specific in the testis. The results imply that positive selection increased K5UTR and structural alteration rate of a certain fraction of genes as well as Ka. We found that both positive and negative selection can act on the 5'UTR sequences.
通过使用人类和食蟹猴的cDNA序列，研究了5'-非翻译区（UTR）的替换率和结构差异。由于UTR中的功能限制比编码序列中的功能限制弱，人类和猕猴之间的差异将为5'UTR中的核苷酸替换率和结构差异提供一个很好的估计。我们发现，5'UTR中的替换率（K5UTR）平均比同义替换率（Ks）低约10%-20%。然而，睾丸cDNA中的K5UTR和非同义替换率（Ka）均显著高于脑cDNA中的，而Ks没有差异。此外，计算机分析显示，与人类cDNA相比，27%（169/622）的猕猴睾丸cDNA在5'UTR中具有改变的外显子-内含子结构。外显子改变的cDNA比例在睾丸cDNA中显著高于脑cDNA。我们通过逆转录酶-聚合酶链反应证实，5'UTR中约三分之一（6/16）的计算机“猕猴特异性”外显子在睾丸中确实是猕猴特异性的。结果表明，正选择增加了K5UTR以及一定比例基因的结构改变率和Ka。我们发现正选择和负选择都可以作用于5'UTR序列。
