DNA methylation site loss for plasticity-led novel trait genetic fixation

T Takafumi Katsumura (Department of Anatomy, Kitasato University School of Medicine) S Suguru Sato (Department of Biological Sciences, Kitasato University School of Science) K Kana Yamashita (Department of Biological Sciences, Kitasato University School of Science) S Shoji Oda (Department of Integrated Biosciences, The University of Tokyo) T Takashi Gakuhari (Institute of Human and Social Sciences, Kanazawa University) S Shodai Tanaka (Department of Biological Sciences, Kitasato University School of Science) K Kazuko Fujitani (Molecular Biology Research Center, Kitasato University School of Medicine) T Toshiyuki Nishimaki (Department of Anatomy, Kitasato University School of Medicine) T Tadashi Imai (Production Engineering Division, Fisheries Technology Institute, Japan Fisheries Research and Education Agency) Y Yasutoshi Yoshiura (Production Engineering Division, Fisheries Technology Institute, Japan Fisheries Research and Education Agency) H Hirohiko Takeshima (Department of Marine Biology, Tokai University School of Biological Sciences) Y Yasuyuki Hashiguchi (Department of Biology, Faculty of Medicine, Osaka Medical and Pharmaceutical University) Y Yoichi Sekita (Department of Biosciences, Kitasato University School of Science) H Hiroshi Mitani (Department of Integrated Biosciences, The University of Tokyo) M Motoyuki Ogawa (Department of Anatomy, Kitasato University School of Medicine) H Hideaki Takeuchi (Department of Biological Science, Graduate School of Natural Science and Technology, Okayama University) H Hiroki Oota (Department of Anatomy, Kitasato University School of Medicine)

Abstract

Phenotypic plasticity allows organisms to adapt traits in response to environmental changes, yet the molecular basis by which such plastic traits become genetically fixed remains unclear. Here, we investigated gut-length plasticity in medaka fish ( Oryzias latipes ) through genome-wide methylation profiling, CRISPR/Cas9-mediated deletion, and population genomic analyses. We found that seasonal methylation of CpG sites upstream of the Plxnb3 is correlated with gut-length plasticity, and deletion of this region abolishes plasticity. Additionally, standing variation in Ppp3r1 is associated with genetically fixed longer gut length in populations lacking plasticity. These results suggest that loss of epigenetic regulation via CpG site reduction triggers the genetic fixation of novel traits. Our findings provide molecular evidence linking epigenetic plasticity and genetic assimilation, advancing understanding of plasticity-led evolution in natural populations.

Article Details

Volume / Issue Vol. 123, Issue 13
Published March 31, 2026
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (17)

T

Takafumi Katsumura

Department of Anatomy, Kitasato University School of Medicine

S

Suguru Sato

Department of Biological Sciences, Kitasato University School of Science

K

Kana Yamashita

Department of Biological Sciences, Kitasato University School of Science

S

Shoji Oda

Department of Integrated Biosciences, The University of Tokyo

T

Takashi Gakuhari

Institute of Human and Social Sciences, Kanazawa University

S

Shodai Tanaka

Department of Biological Sciences, Kitasato University School of Science

K

Kazuko Fujitani

Molecular Biology Research Center, Kitasato University School of Medicine

T

Toshiyuki Nishimaki

Department of Anatomy, Kitasato University School of Medicine

T

Tadashi Imai

Production Engineering Division, Fisheries Technology Institute, Japan Fisheries Research and Education Agency

Y

Yasutoshi Yoshiura

Production Engineering Division, Fisheries Technology Institute, Japan Fisheries Research and Education Agency

H

Hirohiko Takeshima

Department of Marine Biology, Tokai University School of Biological Sciences

Y

Yasuyuki Hashiguchi

Department of Biology, Faculty of Medicine, Osaka Medical and Pharmaceutical University

Y

Yoichi Sekita

Department of Biosciences, Kitasato University School of Science

H

Hiroshi Mitani

Department of Integrated Biosciences, The University of Tokyo

M

Motoyuki Ogawa

Department of Anatomy, Kitasato University School of Medicine

H

Hideaki Takeuchi

Department of Biological Science, Graduate School of Natural Science and Technology, Okayama University

H

Hiroki Oota

Department of Anatomy, Kitasato University School of Medicine