The master male sex determinant Gdf6Y of the turquoise killifish arose through allelic neofunctionalization

Annekatrin Richter (), Hanna Mörl, Maria Thielemann, Markus Kleemann, Raphael Geißen, Robert Schwarz, Carolin Albertz, Philipp Koch, Andreas Petzold, Torsten Kroll, Marco Groth, Nils Hartmann, Amaury Herpin and Christoph Englert ()
Additional contact information
Annekatrin Richter: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Hanna Mörl: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Maria Thielemann: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Markus Kleemann: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Raphael Geißen: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Robert Schwarz: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Carolin Albertz: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Philipp Koch: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Andreas Petzold: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Torsten Kroll: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Marco Groth: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Nils Hartmann: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Amaury Herpin: INRAE, UR1037 Laboratory of Fish Physiology and Genomics, Campus de Beaulieu
Christoph Englert: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Although sex determination is a fundamental process in vertebrate development, it is very plastic. Diverse genes became major sex determinants in teleost fishes. Deciphering how individual sex-determining genes orchestrate sex determination can reveal new actors in sexual development. Here, we demonstrate that the Y-chromosomal copy of the TGF-β family member gdf6 (gdf6Y) in Nothobranchius furzeri, an emerging model organism in aging research, gained the function of the male sex determinant through allelic diversification while retaining the skeletal developmental function shared with the X-chromosomal gdf6 allele (gdf6X). Concerning sex determination, gdf6Y is expressed by somatic supporting cells of the developing testes. There it induces the male sex in a germ cell-independent manner in contrast to sex determination in zebrafish and the medaka. Looking for downstream effectors of Gdf6Y, we identified besides TGF-β signaling modulators, especially the inhibitor of DNA binding genes id1/2/3, the mRNA decay activator zfp36l2 as a new GDF6 signaling target.

Date: 2025
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DOI: 10.1038/s41467-025-55899-7

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