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Phylogenomic and comparative genomic analyses support a single evolutionary origin of flatfish asymmetry

Matters Arising to this article was published on 27 May 2024

The Original Article was published on 19 April 2021

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Fig. 1: Phylogenetic relationships, divergence times and support values for the two competing hypotheses.
Fig. 2: Hypothesized molecular mechanisms underlying flatfish asymmetric development.

Data availability

All newly sequenced data are available from NCBI under the BioProject accession number PRJNA862198. Detailed taxonomic sampling information and phylogenetic datasets are available in the Figshare digital repository7 (see also Supplementary Information). Source data are provided with this paper.

Code availability

We conducted analyses using single commands from publicly available software. All settings are fully reported in the Supplementary Information.


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The computational work for this project was conducted at the University of Oklahoma Supercomputing Center for Education & Research (OSCER). Funding for the project was secured through grants from the National Science Foundation (NSF; DEB-1932759 and DEB-2225130 to R.B., DEB-2015404 and DEB-2144325 to D.A. and DEB-1541554 to G.O.). Additional financial support was provided by the Office of the Vice President for Research and Partnerships, as well as the Office of the Provost at the University of Oklahoma.

Author information

Authors and Affiliations



E.D.R. and R.B.-R. conceived and supervised the project. E.D.R., R.B.-R., K.E.C., W.T.W., J.J.P., M.W., J.M.D.A., J.T.W., M.D.S., O.D.D., G.O. and D.A. collected samples. E.D.R., R.B.-R., U.R.P., M.F., L.C.H., G.C.W., G.O. and D.A. designed and performed bioinformatic analyses. E.D.R., R.B.-R. and M.F. wrote the manuscript. All authors have read, revised and approved the final manuscript.

Corresponding authors

Correspondence to Emanuell Duarte-Ribeiro or Ricardo Betancur-R.

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Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Genetics thanks Jeramiah Smith and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended Data Fig. 1 Species tree for Carangaria estimated with ASTRAL-III.

Species tree for Carangaria estimated with ASTRAL-III using gene trees with weakly supported nodes (bootstrap values [BS] <20%) collapsed into polytomies to reduce the effects of gene-tree error. Gene trees were estimated using IQ-TREE (HM; GTR + G) based on newly sequenced data that covers 990 loci and 389 species. Collapsing gene-tree branches with low support helped reduce the negative effects of gene-tree estimation error, successfully resolving flatfish monophyly (FM [BS 76%]; green arrow) using the complete dataset. Tree files with tip labels and support values are available from the Figshare digital repository.

Extended Data Fig. 2 Schematic representation of the two alternative foreground schemes used to identify positively selected genes in flatfishes using the aBSREL model in HyPhy.

a, Stem flatfishes, which aimed to detect genes responsible for the initial break of symmetry in the single branch leading to all extant flatfish species. b, Crown flatfishes, which aimed to detect genes responsible for further adaptations experienced later in the flatfish radiation.

Extended Data Fig. 3 Amino acid alignments highlighting substitutions (in purple) claimed to be Pleuronectoidei-specific by LEA1.

By adding sequences from Psettodes and other non-flatfish carangarians into the alignments, we show that three out of the four Pleuronectoidei-specific substitutions discussed by the authors are in fact shared with Psettodoidei or other non-flatfish carangarian species. These include two missense substitutions in the musculature development-related gene sgca, which the authors suggest is related to the formation of the flat phenotype. Both substitutions are shared with Polydactylus sextarius, a symmetrical carangarian species, and, therefore, may not necessarily explain the evolution of the flatfish thin musculature. The hoxd12a substitution is shared between Pleuronectoidei and Psettodoidei. This gene is involved in the development of the flatfish dorsal fin, an important locomotion adaptation that improves their maneuverability in the benthic environment, and that may provide additional evidence for the single origin of the asymmetric body plan.

Supplementary information

Supplementary Information

Supplementary Fig. 1–3 and Supplementary Notes 1–4.

Reporting Summary

Source data

Source Data Fig. 1

Source phylogenetic trees.

Source Data Fig. 2

List of detected PSGs in the stem and crown flatfishes.

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Duarte-Ribeiro, E., Rosas-Puchuri, U., Friedman, M. et al. Phylogenomic and comparative genomic analyses support a single evolutionary origin of flatfish asymmetry. Nat Genet 56, 1069–1072 (2024).

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