Medaka fish without functional Hmgn2 genes were unable to tell apart simple shapes, highlighting a new role for this regulatory gene.
The medaka, commonly referred to as the Japanese rice fish (Oryzias latipes), serves as an important model organism in biological research and is also a favored aquarium fish. While extensive studies have been conducted to explore various aspects of the medaka, there is still much to uncover, particularly regarding its genetic makeup.
A research group led by Assistant Professor Saori Yokoi from the Faculty of Pharmaceutical Sciences at Hokkaido University has identified a distinct evolutionary variant of the Hmgn2 gene in medaka, which affects the species’ shape preference. The results of their study were published in the journal Communications Biology.
“We discovered the Hmgn2 variant, named oHmgn2, while researching genes expressed in the medaka brain with unclear functions,” explained Yokoi. “HMGN proteins are essential for chromatin structure changes and the regulation of gene expression in various vertebrates.”
oHmgn2 was chosen for the study due to its unique expression pattern in medaka brains. Upon confirming that the gene encodes an HMGN protein, the RNA sequencing of oHmgn2 revealed it to be 99 base pairs shorter than Hmgn2 in other vertebrates. An evolutionary analysis confirmed that oHmgn2 is indeed a distinct variant.
“One of the most notable differences is the localization of oHmgn2 in the nucleolus, the area within the nucleus where DNA is transcribed into RNA,” elaborated Yokoi. “oHmgn2 is believed to interact less strongly with DNA-binding proteins known as histones compared to typical interactions, which helps explain its localization.”
The expression of oHmgn2 is concentrated in the neurogenic regions of the brain, and the team observed signs that it plays a role in the function of neural progenitor cells. Knockout experiments indicated that the absence of functional oHmgn2 interfered with the development of the telencephalon—the brain region related to the cerebrum and frontal lobes in humans.
Interestingly, wild type medaka show a preference for triangles over circles, spending more time in the maze arm associated with triangles. In contrast, medaka lacking oHmgn2 do not exhibit this preference, demonstrating a challenge in recognizing shapes.
“Our research has demonstrated that the oHmgn2 gene is a crucial factor in the molecular evolution of brain development and cognitive abilities in medaka,” concluded Yokoi. “Future studies will focus on uncovering how oHmgn2 influences shape recognition in these fish.
