Tokyo Institute of Technology sheds light on stomach loss in agastric fish: Four genes are co-deleted

A research group led by Associate Professor Akira Kato, Graduate Student Chihiro Ota, and Assistant Professor Ayumi Nagashima of the School of Life Science and Technology, Professor Masayuki Komada of the Cell Biology Center, Institute of Innovative Research at Tokyo Institute of Technology, and researchers at the Atmosphere and Ocean Research Institute, the University of Tokyo, Shizuoka University, Mayo Clinic College of Medicine & Science (USA), and other institutions have announced their research findings showing that four common genes are newly co-deleted or pseudogenized in agastric fishes of various lineages. This was found through a comprehensive comparison of the genome databases of 11 agastric fish species and 12 gastric fish species. It was also revealed that various lineages of fish have independently lost their stomachs. The findings are expected to contribute to the advancement in understanding the convergent genomic changes associated with organ loss and were published in the international journal Communications Biology on April 3.

Actinopterygii, the largest group of fishes, consists of 44 orders, 453 families and about 30,000 species, including agastric lineages, in which the stomach is absent from the gastrointestinal tract. These species are scattered in multiple orders, such as Cypriniformes and Tetraodontiformes, indicating that the stomach was lost in each lineage independently. Previous studies have estimated that 7% of families and 20%−27% of species in Actinopterygii are agastric and that at least 15 independent stomach loss events have occurred during evolution. Stomach loss is caused by some change in gene function, but the stomach loss itself also causes further genomic changes, and deletions of four genes (atp4a, atp4b, pgc and pga2) responsible for gastric acid secretion and gastric digestive enzymes were reported in various agastric species.

Previously, a group of scientists from Tokyo Institute of Technology and Mayo Clinic College of Medicine & Science used pufferfish, and a research group of the Atmosphere and Ocean Research Institute, the University of Tokyo used eels to study solute carrier family 26 (Slc26), which contributes to freshwater and seawater adaptation in fish. Comparison of the results of the two groups revealed that the gene encoding a transporter of the Slc26 family (slc26a9) is present in the gastric eel, rainbow trout and three-spined stickleback but not present in agastric pufferfish, zebrafish and Japanese medaka, indicating that other genes may be absent in agastric fishes.

In this study, they compared the genome databases of 11 agastric fish species (including zebrafish, Japanese medaka, wrasse and pufferfish) and 12 gastric fish species (including catfish, rainbow trout, Nile tilapia and three-spined stickleback) comprehensively and found that four new genes (slc26a9, kcne2, cldn18a and vsig1) were deleted or pseudogenized. It was also confirmed that genes lost in agastric fishes were expressed in the stomach of gastric fishes. The functions of a total of eight genes commonly absent in agastric fish were classified into gastric acid secretion, digestive enzymes and intercellular adhesion/barrier formation. There are other membrane transporter-related genes involved in gastric acid secretion, but all of the genes absent in the agastric fishes were known to function in the membranes of cells inside the stomach. Monotremes (such as platypus and echidnas), which are primitive mammals, also have vestigial stomachs.

Exploration of the genomic data of these animals for the genes lost in agastric fishes showed that vsig1 was pseudogenized in platypus and kcne2 was deleted in echidna. They also found that atp4a, atp4b, pgc and pga (homologous gene of pga2) were deleted or pseudogenized in platypus and echidna. These findings contribute to the advancement in understanding the convergent genomic changes associated with organ loss and have potential applications in understanding the diverse environmental adaptation strategies of aquatic animals and in conserving biodiversity.

Kato said, "Advances in genome science have led to the decoding and publication of the genome sequences of several thousand vertebrate species. The amount of data is enormous, but if you read it from your own unique perspective, you may discover the unexpected. The starting point of this study was a simple question from a conversation, 'There is an interesting gene called slc26a9. Do you know if fish have it?' I researched and discussed with my colleagues to find the answer to this question and could finally make an interesting discovery."

Journal Information
Publication: Communications Biology
Title: Convergent gene losses and pseudogenizations in multiple lineages of stomachless fishes
DOI: 10.1038/s42003-024-06103-x