A complex genetic architecture in zebrafish relatives Danio quagga and D. kyathit underlies development of stripes and spots
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Abstract
Vertebrate pigmentation is a fundamentally important, multifaceted phenotype. Zebrafish, Danio rerio , has been a valuable model for understanding genetics and development of pigment pattern formation due to its genetic and experimental tractability, advantages that are shared across several Danio species having a striking array of pigment patterns. Here, we use the sister species D . quagga and D . kyathit , with stripes and spots, respectively, to understand how natural genetic variation impacts phenotypes at cellular and organismal levels. We first show that D . quagga and D . kyathit phenotypes resemble those of wild-type D . rerio and several single locus mutants of D . rerio , respectively, in a morphospace defined by pattern variation along dorsoventral and anteroposterior axes. We then identify differences in patterning at the cellular level between D . quagga and D . kyathit by repeated daily imaging during pattern development and quantitative comparisons of adult phenotypes, revealing that patterns are similar initially but diverge ontogenetically. To assess the genetic architecture of these differences, we employ reduced-representation sequencing of second-generation hybrids. Despite the similarity of D . quagga to D . rerio , and D . kyathit to some D . rerio mutants, our analyses reveal a complex genetic basis for differences between D . quagga and D . kyathit , with several quantitative trait loci contributing to variation in overall pattern and cellular phenotypes, epistatic interactions between loci, and abundant segregating variation within species. Our findings provide a window into the evolutionary genetics of pattern-forming mechanisms in Danio and highlight the complexity of differences that can arise even between sister species. Further studies of natural genetic diversity underlying pattern variation in D . quagga and D . kyathit should provide insights complementary to those from zebrafish mutant phenotypes and more distant species comparisons.
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Of the remaining combinations, six (16.7 % of total) showed variant stripe pattern, but with enough variability that phenotypes could also overlap with those of control hybrids, suggesting genetic polymorphisms in modifier loci within species.
“Of the remaining combinations, six (16.7 % of total) showed variant stripe pattern (circles with dashed white outlines in Fig. 5A), but with enough variability that phenotypes could also overlap with those of control hybrids, suggesting genetic polymorphisms in modifier loci within species48.”
From Genomic and genetic insights into speciation and pigment pattern diversification in <i>Danio</i> fishes (2025) · cites this paper as [48]
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Cited by
Sorted by citations
Huang, D., Kapadia, E. H., Liang, Y., Shriver, L. P., Dai, S., Patti, G. J., Humbel, B. M., Laudet, V., & Parichy, D. M. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2424180122 · Cited by 15 · see citing works
Self-citationLu, J., Podobnik, M., Huang, J., McCluskey, B. M., McCarthy, S. A., Wood, J., Collins, J., Torrance, J., Sims, Y., Gao, D., et al. (2025) · doi:10.1101/2025.10.17.682988 · Cited by 4 · see citing works
Self-citationZebrafish relatives as models for functional comparative genetics and genomics
Podobnik, M., Lu, Y., Irion, U., & Currie, P. D. (2026) · Nature Reviews Genetics · doi:10.1038/s41576-026-01007-4 · Cited by 1 · see citing works
- Authors
- McCluskey, B. M., Uji, S., Mancusi, J. L., Postlethwait, J. H., & Parichy, D. M.
- Affiliations
- University of Virginia (US)
- Japan Fisheries Research and Education Agency (JP)
- University of Oregon (US)
- Corresponding author
- Parichy, David M.
- Venue
- PLOS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2021-04-26
- Volume
- 17
- Issue
- 4
- Pages
- e1009364
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC8102007
- OpenAlex
- W3158597610
- Cited by
- 19
- References
- 4
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 6
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Update notices
- new_version (2021-05-06)
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of General Medical Sciences (R35 GM122471, F32 GM119202, T32 GM07413)
- National Institutes of Health Office of the Director (R01 OD011116)
- Japan Fisheries Research and Education Agency
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- zebrafish, pigment pattern formation, natural genetic variation, quantitative trait loci, epistasis, hybrid mapping, evolutionary genetics, zebrafish mutants
- MeSH terms
- Animals, Cyprinidae, Embryo, Nonmammalian, Melanophores, Metamorphosis, Biological, Phenotype, Phylogeny, Skin Pigmentation, Species Specificity, Zebrafish, Gene Expression Regulation, Developmental, Embryonic Development
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