Kitano Group / Ecological Genetics Laboratory

Functional mutations in the thyroid-stimulating hormone receptor in natural stickleback populations at sites identical to human disease-causing mutations

Jun Kitano, Mana Sato, Hiyu Kanbe, Genta Okude, Asano Ishikawa, Yukinori Kazeto & Takashi Makino

BMC Ecology and Evolution (2025) 98 DOI:10.1186/s12862-025-02440-5

This study examined whether mutations that cause thyroid disease in humans could help identify functional mutations in natural stickleback populations. The researchers found that several Japanese stickleback populations carry non-synonymous mutations in the thyroid-stimulating hormone receptor (Tshr)2 gene. Functional assays revealed that amino acid substitutions at sites corresponding to human loss-of-function or gain-of-function mutations similarly reduced or enhanced receptor activity. Thus, we discovered natural populations carrying mutations similar to those that cause human disease. Further research is needed to determine whether these mutations are deleterious or adaptive in their habitats.

Figure: Hariyo (a freshwater population of the genus Gasterosteus, currently found in Gifu and Shiga Prefectures, and formerly inhabiting Mie Prefecture, Japan) possessed a mutation in the thyroid-stimulating hormone receptor (TSHR) gene at an identical site where mutations cause human disease.
Photo courtesy of Yasuyuki Hata.