Evolutionary expression differences of creatine synthesis-related genes: Implications for skeletal muscle metabolism in fish

Andreas Borchel,Marieke Verleih,Tom Goldammer,Alexander Rebl,Carsten Kühn

doi:10.1038/s41598-019-41907-6

Andreas Borchel, Marieke Verleih + Show 3 more

Open Access

https://doi.org/10.1038/s41598-019-41907-6

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Abstract

The creatine/phosphocreatine system is the principal energy buffer in mammals, but is scarcely documented in fish. We measured the gene expression of major enzymes of this system, glycine amidinotransferase (GATM), guanidinoacetate N-methyltransferase (GAMT) and muscle-type creatine kinase (CKM) in kidney, liver, and muscle tissues of fish and mammals. CKM was expressed strongly in the muscles of all examined species. In contrast, GATM and GAMT were strongly expressed in the muscle tissue of fish, but not of mammals. This indicates that creatine synthesis and usage are spatially separated in mammals, but not in fish, which is supported by RNA-Seq data of 25 species. Differences in amino acid metabolism along with methionine adenosyltransferase gene expression in muscle from fishes but not mammals further support a central metabolic role of muscle in fish, and hence different organization of the creatine/phosphocreatine biosynthesis system in higher and lower vertebrates.

Highlights

The creatine/phosphocreatine system is the principal energy buffer in mammals, but is scarcely documented in fish
We isolated >300-bp fragments of genes encoding guanidinoacetate N-methyltransferase (GAMT), GATM, and CKM from four teleost species based on a PCR approach with degenerated primer oligonucleotides
The GAMT sequence from whitefish was complemented with contigs that were generated by transcriptome sequencing of maraena whitefish and was verified via PCR and DNA sequencing

Summary

Introduction

The creatine/phosphocreatine system is the principal energy buffer in mammals, but is scarcely documented in fish. We measured the gene expression of major enzymes of this system, glycine amidinotransferase (GATM), guanidinoacetate N-methyltransferase (GAMT) and muscle-type creatine kinase (CKM) in kidney, liver, and muscle tissues of fish and mammals. GATM and GAMT were strongly expressed in the muscle tissue of fish, but not of mammals. This indicates that creatine synthesis and usage are spatially separated in mammals, but not in fish, which is supported by RNA-Seq data of 25 species. Contrary to the expectations for GATM and GAMT expression in the kidneys and liver of trout, the skeletal muscle as profiteer of creatine comprises higher transcript amounts of these genes[8]. We analyze gene-expression patterns from several other species based on publicly available RNA-Seq data to compare creatine systems between the vertebrate taxa pisces, amphibia, reptilia, aves, and mammalia

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