Repeatability of protein structural evolution following convergent gene fusions

Naoki Konno (), Keita Miyake, Satoshi Nishino, Kimiho Omae, Haruaki Yanagisawa, Saburo Tsuru, Yuki Nishimura, Masahide Kikkawa, Chikara Furusawa and Wataru Iwasaki
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Naoki Konno: The University of Tokyo
Keita Miyake: The University of Tokyo
Satoshi Nishino: The University of Tokyo
Kimiho Omae: The University of Tokyo
Haruaki Yanagisawa: The University of Tokyo
Saburo Tsuru: The University of Tokyo
Yuki Nishimura: The University of Tokyo
Masahide Kikkawa: The University of Tokyo
Chikara Furusawa: The University of Tokyo
Wataru Iwasaki: The University of Tokyo

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Convergent evolution of proteins provides insights into repeatability of genetic adaptation. While local convergence of proteins at residue or domain level has been characterized, global structural convergence by inter-domain/molecular interactions remains largely unknown. Here we present structural convergent evolution on fusion enzymes of aldehyde dehydrogenases (ALDHs) and alcohol dehydrogenases (ADHs). We discover BdhE (bifunctional dehydrogenase E), an enzyme clade that emerged independently from the previously known AdhE family through distinct gene fusion events. AdhE and BdhE show shared enzymatic activities and non-overlapping phylogenetic distribution, suggesting common functions in different species. Cryo-electron microscopy reveals BdhEs form donut-like homotetramers, contrasting AdhE’s helical homopolymers. Intriguingly, despite distinct quaternary structures and

Date: 2025
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DOI: 10.1038/s41467-025-63898-x

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