February 21, 2022
February 21, 2022

Discovery of a novel natriuretic peptide (CNP4b) in Japanese eels

Decipher hidden evolution and functional differentiation of hormones using primitive teleost

Dr. Takehiro Tsukada (left)
Ms. Ami Saito (right)
A research group consisting of Dr. Takehiro Tsukada of the Department of Biomolecular Science, Faculty of Science, Toho University, and several other members from the same and other universities, have discovered a novel C-type natriuretic peptide (CNP) in Japanese eel, named CNP4b. The discovery of this hormone suggests that the natriuretic peptide family diversified during vertebrate evolution and then underwent functional differentiation. This hormone molecule has become a pseudogene in Japanese medaka and pufferfish (a group of percomorpha). It was first discovered by studying eels, which is one of primitive teleost. The results were published in the journal Cell and Tissue Research on 16 February 2022.
Dr. Takehiro Tsukada (left)
Ms. Ami Sato (right)
Dr. Tetsuya Muramoto of Department of Biology, Faculty of Science, Toho University, has published the results of a research collaboration with a research team led by Professor Nicholas D. Lakin at the Oxford University in the UK. The team has revealed a new finding that ADP-ribosylation, a modification that adds ADP to serine in “histone proteins, which functions like a spool to store DNA in the nucleus”, is involved in regulating DNA repair and cell cycle progression. This research result is expected to provide an in-depth illumination on the mechanism of cancer development and DNA repair pathways. This research was published in the British scientific journal “Nature Communications” on January 13, 2022.
Key points
  • A new natriuretic peptide (CNP4b) was discovered in Japanese eel.
  • This research clarified the relationship between molecular evolution and functional differentiation of natriuretic peptides.
  • The in situ hybridization chain reaction method using fluorescently labeled short hairpin DNA was demonstrated for the first time in non-vertebrate species.
The natriuretic peptide family consists of ANP, BNP, and CNP. ANP and BNP are hormones secreted by the heart to regulate blood pressure. CNP is a hormone produced in the brain, but its central function remains unclear. A research group led by Dr. Tsukada has shown that CNP genes have diversified during vertebrate evolution. In particular, four CNP genes (CNP1-4) have been found in teleost (compared to one in mammals), suggesting that the hormone is important for brain function in fish. In this presentation, they report the discovery of a fifth CNP gene (CNP4b) in Japanese eels. The research group has also found that other teleosts do not possess CNP4b gene, and that CNP4 compensates a function of CNP4b. This study sheds light on the scientifically hidden molecular evolution of the natriuretic peptide family and provides important data on the relationship between genetic diversification and functional differentiation.

Evolution of natriuretic peptide family in teleost

Cell and Tissue Research (Published online on February 16, 2022)

Gene duplication of C-type natriuretic peptide-4 (CNP4) in teleost lineage elicits subfunctionalization of ancestral CNP

Yukitoshi Katayama, Ami Saito, Maho Ogoshi, Yousuke Tsuneoka, Takao Mukuda,Morio Azuma, Makoto Kusakabe, Yoshio Takei, Takehiro Tsukada

DOI Number:


@ Toho University