Evidence map›Paper›PMID 40983608›Full record

ArticleNature communications2025

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, Wataru Iwasaki

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Naoki KonnoDepartment of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. konno-naoki555@g.ecc.u-tokyo.ac.jp.
Keita MiyakeDepartment of General Systems Studies, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo, 153-8902, Japan.
Satoshi NishinoDepartment of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba, 277-0882, Japan.ORCID http://orcid.org/0009-0007-2070-7678
Kimiho OmaeDepartment of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba, 277-0882, Japan.
Haruaki YanagisawaDepartment of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Saburo TsuruUniversal Biology Institute, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.ORCID http://orcid.org/0000-0002-7182-1637
Yuki NishimuraDepartment of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba, 277-0882, Japan.ORCID http://orcid.org/0000-0002-7990-1316
Masahide KikkawaDepartment of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.ORCID http://orcid.org/0000-0001-7656-8194
Chikara FurusawaUniversal Biology Institute, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Wataru IwasakiDepartment of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Funding

Japan Agency for Medical Research and Development (AMED) JP24ama121002MEXT | Japan Science and Technology Agency (JST) JPMJGX23B2MEXT | Japan Society for the Promotion of Science (JSPS) 21H05247MEXT | Japan Society for the Promotion of Science (JSPS) 21H05248MEXT | Japan Society for the Promotion of Science (JSPS) 22J20318MEXT | Japan Society for the Promotion of Science (JSPS) 24H00870MEXT | Japan Society for the Promotion of Science (JSPS) JP22H04925MEXT | JST | Exploratory Research for Advanced Technology (ERATO) JPMJER1902
6 · The paper itself

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 < 30% amino acid sequence identity, both enzymes forms resemble dimeric structure units by ALDH-ADH interactions via convergently elongated loop structures. These findings suggest convergent gene fusions recurrently led to substrate channeling evolution to enhance two-step reaction efficiency. Our study unveils structural convergence at inter-domain/molecular level, expanding our knowledges on patterns behind molecular evolution exploring protein structural universe.

Indexed as

Alcohol DehydrogenaseAldehyde DehydrogenaseEvolution, MolecularGene FusionCryoelectron MicroscopyModels, MolecularPhylogenyProtein ConformationAlcohol DehydrogenaseAldehyde Dehydrogenase

Identifiers

PMID40983608
PMCPMC12454647

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.