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MBE Advance Access published online on August 24, 2005

Molecular Biology and Evolution, doi:10.1093/molbev/msi243
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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 August 3, 2005

Research Article

Structural and Functional Evolution of Three Cardiac Natriuretic Peptides

Koji Inoue 1*, Takashi Sakamoto 2, Shinya Yuge 1, Hozi Iwatani 3, Sayaka Yamagami 4, Makiko Tsutsumi 5, Hiroshi Hori 5, Maria Carmela Cerra 6, Bruno Tota 6, Norio Suzuki 4, Nobuaki Okamoto 2, and Yoshio Takei 1

1 Ocean Research Institute, The University of Tokyo, Minamidai, Nakano, Tokyo 164-8639, Japan
2 Department of Aquatic Biosciences, Tokyo University of Marine Science and Technology, Minato, Tokyo 108-8477, Japan
3 Fukui Prefectural Inlandwater General Center, Fukui 910-0816, Japan
4 Division of Biological Sciences, Graduate school of Science, Hokkaido University, Sapporo 060-0810, Japan
5 Division of Biological Sciences, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan
6 Departimento di Biologia Cellulare, Università della Calabria, Arcavacata Di Rende (CS), I-87030 Italy

* To whom correspondence should be addressed.
Koji Inoue, E-mail: inouek{at}ori.u-tokyo.ac.jp


   Abstract

Natriuretic peptides (NPs) are a group of hormones playing important roles in cardiovascular and osmoregulatory systems in vertebrates. Among the NP subtypes, atrial NP (ANP), B-type NP (BNP) and ventricular NP (VNP) are circulating hormones expressed exclusively in the heart (cardiac NPs). The constitution of cardiac NPs is variable among species of vertebrates. In order to understand the evolutionary and functional significance of such variation, we performed a systematic survey of cardiac NP cDNAs in nine taxonomically diverse teleosts inhabiting environments of varying salinity. The discovery of the co-existence of the ANP, BNP and VNP genes in the eel and rainbow trout suggested that the ancestral teleost had all three cardiac NPs. As the VNP cDNA was undetectable in ayu and six species of Neoteleostei, it is possible that VNP was lost before the divergence of Osmeroidei. The ANP gene was also undetectable in the medaka. Thus, only the BNP gene is universal in species examined in the present study. Synthetic medaka BNP preferentially activated two medaka GC-A-type receptors, suggesting that the three cardiac NPs share the same receptor. However, the regulation of BNP expression may be the most strict because ATTTA repeats in the 3'-untranslated region and the dibasic motif in the ring are conserved among teleosts and tetrapods. Linkage analyses in the rainbow trout located ANP, BNP and VNP genes on the same chromosome, which suggested the generation of the VNP gene by tandem duplication as observed with ANP and BNP genes. If the duplication occurred before the divergence of tetrapods and teleosts, VNP may exist in the tetrapod lineage.

Keywords: natriuretic peptides; guanylyl cyclase; evolution; tandem duplication; linkage mapping.
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