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MBE Advance Access published online on June 8, 2005
Molecular Biology and Evolution, doi:10.1093/molbev/msi187
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© The Author 2005. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org
Accepted May 30, 2005

Research Article

Substitution Rate and Structural Divergence of 5'UTR Evolution: Comparative Analysis Between Human and Cynomolgus Monkey cDNAs

Naoki Osada 1, Makoto Hirata 1, Reiko Tanuma 1, Jun Kusuda 1, Munetomo Hida 2, Yutaka Suzuki 2, Sumio Sugano 2, Takashi Gojobori 3, C.-K. James Shen 4, Chung-I Wu 5, and Katsuyuki Hashimoto 6*

1 Division of Genetic Resources, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Laboratory of Genetic Resources, Bioresource Division, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan
2 Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa-shi, Chiba 277-8562, Japan
3 Center of Information Biology, National Institute of Genetics, Research Organization of Information and Systems, Yata 1111, Mishima, Shizuoka 411-8540, Japan
4 Institute of Molecular Biology, Academia Sinica, 128 Sec. 2, Academia Rd, Nankang, Taipei 115, Taiwan
5 Department of Ecology and Evolution, University of Chicago, 1101 E. 57th Chicago, IL, 60637
6 Division of Genetic Resources, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan

* To whom correspondence should be addressed.
Katsuyuki Hashimoto, E-mail: khashi{at}nih.go.jp


  Abstract

The substitution rate and structural divergence in the 5' untranslated region (UTR) was investigated by using human and cynomolgus monkey cDNA sequences. Due to the weaker functional constraint in the UTR than in the coding sequence (CDS), 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 {approx}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 RT-PCR 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.

Keywords: evolution; substitution rate; 5'UTR; alternative splicing; primates.
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