The Most Developmentally Truncated Fishes Show Extensive Hox Gene Loss and Miniaturized Genomes
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Abstract
The world's smallest fishes belong to the genus Paedocypris. These miniature fishes are endemic to an extreme habitat: the peat swamp forests in Southeast Asia, characterized by highly acidic blackwater. This threatened habitat is home to a large array of fishes, including a number of miniaturized but also developmentally truncated species. Especially the genus Paedocypris is characterized by profound, organism-wide developmental truncation, resulting in sexually mature individuals of <8 mm in length with a larval phenotype. Here, we report on evolutionary simplification in the genomes of two species of the dwarf minnow genus Paedocypris using whole-genome sequencing. The two species feature unprecedented Hox gene loss and genome reduction in association with their massive developmental truncation. We also show how other genes involved in the development of musculature, nervous system, and skeleton have been lost in Paedocypris, mirroring its highly progenetic phenotype. Further, our analyses suggest two mechanisms responsible for the genome streamlining in Paedocypris in relation to other Cypriniformes: severe intron shortening and reduced repeat content. As the first report on the genomic sequence of a vertebrate species with organism-wide developmental truncation, the results of our work enhance our understanding of genome evolution and how genotypes are translated to phenotypes. In addition, as a naturally simplified system closely related to zebrafish, Paedocypris provides novel insights into vertebrate development.
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The genome compaction previously reported in Paedocypris extends to progenetic miniatures more broadly, while it is not a feature of proportioned dwarfism.
“This extends the genome compaction previously reported in Paedocypris (18) to progenetic miniatures more broadly, while confirming that it is not a feature of proportioned dwarfism.”
From Convergent genome streamlining accompanies independent miniaturization in the world’s smallest fishes (2026) · cites this paper as [18]
The Results (‘Genome Miniaturization through Intron Shortening’) report substantially smaller genomes in two Paedocypris species. But the Discussion says genome sizes of proportionate dwarfs remain to be examined and does not establish genome compaction in progenetic miniatures beyond Paedocypris. The broader extension and the asserted absence of compaction in proportionate dwarfs are therefore unsupported. (LLM, conf=0.90)
Experimental — accuracy not yet measuredChanges in intron lengths have been shown to be a significant part of genomic truncations and expansions, such as severe intron shortening in Paedocypris or intron expansion in zebrafish.
“Changes in the intron lengths have been shown to be a significant part of genomic truncations and expansions, such as a severe intron shortening in another miniature fish species, Paedocypris35, or an intron expansion in zebrafish36.”
From Hybrid genome assembly and annotation of Danionella translucida (2019) · cites this paper as [35]
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High-throughput functional genomics using CRISPR-Cas9
Shalem, O., Sanjana, N. E., & Zhang, F. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3899 · Cited by 1,233 · see citing works
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Britz, R., Conway, K. W., & Rüber, L. (2021) · Scientific Reports · doi:10.1038/s41598-021-97600-0 · Cited by 53 · see citing works
Self-citationHybrid genome assembly and annotation of Danionella translucida
Kadobianskyi, M., Schulze, L., Schuelke, M., & Judkewitz, B. (2019) · Scientific Data · doi:10.1038/s41597-019-0161-z · Cited by 36 · see citing works
Conway, K. W., M. Kubicek, K., & Britz, R. (2021) · Developmental Dynamics · doi:10.1002/dvdy.280 · Cited by 25 · see citing works
Self-citationSudasinghe, H., Matschiner, M., Britz, R., Conway, K. W., Tan, H. H., Salzburger, W., Peichel, C. L., & Rüber, L. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2614605123
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- Authors
- Malmstrøm, M., Britz, R., Matschiner, M., Tørresen, O. K., Hadiaty, R. K., Yaakob, N., Tan, H. H., Jakobsen, K. S., Salzburger, W., & Rüber, L.
- Affiliations
- University of Oslo (NO)
- Natural History Museum (GB)
- Indonesian Institute of Sciences (ID)
- Forest Research Institute Malaysia (MY)
- National University of Singapore (SG)
- University of Bern (CH)
- Corresponding author
- Malmstrøm, Martin
- ORCID
- Venue
- Genome Biology and Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-03-15
- Volume
- 10
- Issue
- 4
- Pages
- 1088-1103
- ISSN
- 1759-6653 (ISSN-L)
- PMC
- PMC5906920
- OpenAlex
- W2952422846
- Cited by
- 40
- References
- 3
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 10 · 2019: 3 · 2018: 1
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Genome Biology and Evolution (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
- National University of Singapore (submittedVersion, cc-by-nc)
- BORIS (University Library Bern) (submittedVersion, cc-by-nc)
- edoc (University of Basel) (submittedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National University of Singapore (R-154-000-318-112)
- North of England Zoological Society
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- genome streamlining, genome reduction, brain development, skeletal development, vertebrate development, Cypriniformes, whole genome sequencing
- MeSH terms
- Animals, Cyprinidae, Genes, Homeobox, Phylogeny, Zebrafish, Genome, Evolution, Molecular, Body Size
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