The little skate genome and the evolutionary emergence of wing-like fins

Ferdinand Marlétaz; Elisa de la Calle-Mustienes; Rafael D Acemel; Christina Paliou; Silvia Naranjo; Pedro Manuel Martínez-García; Ildefonso Cases; Victoria A Sleight; Christine Hirschberger; Marina Marcet-Houben; Dina Navon; Ali Andrescavage; Ksenia Skvortsova; Paul Edward Duckett; Álvaro González-Rajal; Ozren Bogdanovic; Johan H Gibcus; Liyan Yang; Lourdes Gallardo-Fuentes; Ismael Sospedra; Javier Lopez-Rios; Fabrice Darbellay; Axel Visel; Job Dekker; Neil Shubin; Toni Gabaldón; Tetsuya Nakamura; Juan J Tena; Darío G Lupiáñez; Daniel S Rokhsar; José Luis Gómez-Skarmeta

doi:10.1038/s41586-023-05868-1

The little skate genome and the evolutionary emergence of wing-like fins

Ferdinand Marlétaz^* (Corresponding Author)
, Elisa de la Calle-Mustienes
, Rafael D Acemel
, Christina Paliou
, Silvia Naranjo
, Pedro Manuel Martínez-García
, Ildefonso Cases
, Victoria A Sleight
, Christine Hirschberger
, Marina Marcet-Houben
, Dina Navon
, Ali Andrescavage
, Ksenia Skvortsova
, Paul Edward Duckett
, Álvaro González-Rajal
, Ozren Bogdanovic
, Johan H Gibcus
, Liyan Yang
, Lourdes Gallardo-Fuentes
, Ismael Sospedra

Javier Lopez-Rios, Fabrice Darbellay, Axel Visel, Job Dekker, Neil Shubin, Toni Gabaldón, Tetsuya Nakamura^* (Corresponding Author), Juan J Tena^* (Corresponding Author), Darío G Lupiáñez^* (Corresponding Author), Daniel S Rokhsar^* (Corresponding Author), José Luis Gómez-Skarmeta

^*Corresponding author for this work

Aberdeen Centre For Environmental Sustainability

University College London
Okinawa Institute of Science and Technology Graduate University
Universidad Pablo de Olavide
CSIC- Andalusian Centre for Developmental Biology (CABD)
Junta de Andalucía
University of Cambridge
Barcelona Supercomputing Centre (BCS-CNS)
The Barcelona Institute of Science and Technology
Rutgers - The State University of New Jersey, New Brunswick
Garvan Institute of Medical Research
University of New South Wales
University of Massachusetts Chan Medical School
Lawrence Berkeley National Laboratory
University of Geneva
US Department of Energy Joint Genome Institute
University of California Merced
Howard Hughes Medical Institute
The University of Chicago
ICREA
Instituto de Salud Carlos III
Berlin Institute for Medical Systems Biology (BIMSB)
University of California at Berkeley
Chan Zuckerberg Biohub

Research output: Contribution to journal › Article › peer-review

55 Citations (Scopus)

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Abstract

Skates are cartilaginous fish whose body plan features enlarged wing-like pectoral fins, enabling them to thrive in benthic environments 1,2. However, the molecular underpinnings of this unique trait remain unclear. Here we investigate the origin of this phenotypic innovation by developing the little skate Leucoraja erinacea as a genomically enabled model. Analysis of a high-quality chromosome-scale genome sequence for the little skate shows that it preserves many ancestral jawed vertebrate features compared with other sequenced genomes, including numerous ancient microchromosomes. Combining genome comparisons with extensive regulatory datasets in developing fins-including gene expression, chromatin occupancy and three-dimensional conformation-we find skate-specific genomic rearrangements that alter the three-dimensional regulatory landscape of genes that are involved in the planar cell polarity pathway. Functional inhibition of planar cell polarity signalling resulted in a reduction in anterior fin size, confirming that this pathway is a major contributor to batoid fin morphology. We also identified a fin-specific enhancer that interacts with several hoxa genes, consistent with the redeployment of hox gene expression in anterior pectoral fins, and confirmed its potential to activate transcription in the anterior fin using zebrafish reporter assays. Our findings underscore the central role of genome reorganization and regulatory variation in the evolution of phenotypes, shedding light on the molecular origin of an enigmatic trait.

Original language	English
Pages (from-to)	495-503
Number of pages	8
Journal	Nature
Volume	616
Early online date	12 Apr 2023
DOIs	https://doi.org/10.1038/s41586-023-05868-1
Publication status	Published - 20 Apr 2023

Bibliographical note

Acknowledgements
We thank R. Schneider, D. Sherwood and the staff of the Marine Biological Laboratory Embryology course for providing laboratory space; L. Bertrand and the staff at Leica Microsystems for microscopy support; D. Remsen, S. Bennett, D. Calzarette, and the staff of the Marine Biological Laboratory and MBL Marine Resources Center for technical and animal husbandry assistance; A. Gillis for support and advice with RNA-seq and skate functional experiments; and A. Shindo for technical support of image analysis.

Data Availability Statement

Raw and processed sequencing data were deposited at the Gene Expression Omnibus (GEO; GSE188980 and GSE190730) and SRA (PRJNA783899). Mouse hindlimb RNA-seq data used for comparative analyses are publicly available at the GEO (GSE104459) and mouse forelimb RNA-seq data at the GEO (GSE136437). Zebrafish and elephant shark bisulphite sequencing data used for comparison were downloaded from NCBI BioProject (PRJNA379367) and the GEO (GSE122723136), respectively. Skate RNA-seq data are publicly available at NCBI BioProject (PRJNA288370 and PRJNA686126).

Funding

T.N., D.N. and A.A. were supported by institutional support provided by the Rutgers University School of Arts and Sciences and the Human Genetics Institute of New Jersey, a Whitman Center Fellowship (Marine Biological Laboratory) and the National Science Foundation under grant no. 2210072. D.N. was further supported by the NIH-IRACDA funded INSPIRE program at Rutgers University; F.M. and D.S.R. by funding from the Okinawa Institute for Science and Technology; D.S.R. by the Marthella Foskett-Brown Chair in Computational Biology; D.G.L. and R.D.A. by a grant from the Deutsche Forschungsgemeinschaft (LU 242672-1) and by a Helmholtz ERC Recognition Award grant from the Helmholtz-Gemeinschaft (ERC-RA1045 0033); R.D.A. and C.P. by EMBO Postdoctoral Fellowships (EMBO ALTF 537-2020 and ALTF 346-2020, respectively); P.M.M.G. by a postdoctoral fellowship from Junta de Andalucía (DOC_00397); J.J.T. and J.L.G.-S. by the European Research Council (ERC, grant no. 740041) and the Spanish Ministerio de Economía y Competitividad (grant no. PID2019-103921GB-I00); J.D. by the NIH grant HG003143; F.M. by the Royal Society (URF\R1\191161); V.A.S. by a Wolfson College Junior Research Fellowship and Marine Biological Laboratory Whitman Early Career Fellowship; J.L.-R. by the Spanish Ministerio de Ciencia e Innovacion (PID2020-113497GB-I00); and A.V. and F.D. by NIH grants R01DE028599 and R01HG003988. Research conducted at the E.O. Lawrence Berkeley National Laboratory was performed under US Department of Energy contract DE-AC02-05CH11231, University of California. J.D. is an investigator of the Howard Hughes Medical Institute.

Funders	Funder number
European Research Council	ERC-RA1045 0033
The Royal Society	URF\R1\191161
Wolfson College Junior Research Fellowship
Marine Biological Laboratory Whitman Early Career Fellowship
National Science Foundation	2210072
National Institutes of Health	HG003143, R01DE028599, R01HG003988
US Department of Energy	DE-AC02-05CH11231
Deutsche Forschungsgemeinschaft	LU 242672-1
EMBO	EMBO ALTF 537-2020, ALTF 346-2020
Junta de Andalucía	DOC_00397
Ministerio de Economía y Competitividad	PID2019-103921GB-I00
Ministerio de Ciencia e Innovación	PID2020-113497GB-I00

Keywords

embryogenesis
evoltionary development biology
evolutionary genetics
genome evolution

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Marletaz_etal_N_The_Little_Skate_VOR
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Cite this

Marlétaz, F., de la Calle-Mustienes, E., Acemel, R. D., Paliou, C., Naranjo, S., Martínez-García, P. M., Cases, I., Sleight, V. A., Hirschberger, C., Marcet-Houben, M., Navon, D., Andrescavage, A., Skvortsova, K., Duckett, P. E., González-Rajal, Á., Bogdanovic, O., Gibcus, J. H., Yang, L., Gallardo-Fuentes, L., ... Gómez-Skarmeta, J. L. (2023). The little skate genome and the evolutionary emergence of wing-like fins. Nature, 616, 495-503. https://doi.org/10.1038/s41586-023-05868-1

Marlétaz, F, de la Calle-Mustienes, E, Acemel, RD, Paliou, C, Naranjo, S, Martínez-García, PM, Cases, I, Sleight, VA, Hirschberger, C, Marcet-Houben, M, Navon, D, Andrescavage, A, Skvortsova, K, Duckett, PE, González-Rajal, Á, Bogdanovic, O, Gibcus, JH, Yang, L, Gallardo-Fuentes, L, Sospedra, I, Lopez-Rios, J, Darbellay, F, Visel, A, Dekker, J, Shubin, N, Gabaldón, T, Nakamura, T, Tena, JJ, Lupiáñez, DG, Rokhsar, DS & Gómez-Skarmeta, JL 2023, 'The little skate genome and the evolutionary emergence of wing-like fins', Nature, vol. 616, pp. 495-503. https://doi.org/10.1038/s41586-023-05868-1

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abstract = "Skates are cartilaginous fish whose body plan features enlarged wing-like pectoral fins, enabling them to thrive in benthic environments 1,2. However, the molecular underpinnings of this unique trait remain unclear. Here we investigate the origin of this phenotypic innovation by developing the little skate Leucoraja erinacea as a genomically enabled model. Analysis of a high-quality chromosome-scale genome sequence for the little skate shows that it preserves many ancestral jawed vertebrate features compared with other sequenced genomes, including numerous ancient microchromosomes. Combining genome comparisons with extensive regulatory datasets in developing fins-including gene expression, chromatin occupancy and three-dimensional conformation-we find skate-specific genomic rearrangements that alter the three-dimensional regulatory landscape of genes that are involved in the planar cell polarity pathway. Functional inhibition of planar cell polarity signalling resulted in a reduction in anterior fin size, confirming that this pathway is a major contributor to batoid fin morphology. We also identified a fin-specific enhancer that interacts with several hoxa genes, consistent with the redeployment of hox gene expression in anterior pectoral fins, and confirmed its potential to activate transcription in the anterior fin using zebrafish reporter assays. Our findings underscore the central role of genome reorganization and regulatory variation in the evolution of phenotypes, shedding light on the molecular origin of an enigmatic trait. ",

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author = "Ferdinand Marl{\'e}taz and \{de la Calle-Mustienes\}, Elisa and Acemel, \{Rafael D\} and Christina Paliou and Silvia Naranjo and Mart{\'i}nez-Garc{\'i}a, \{Pedro Manuel\} and Ildefonso Cases and Sleight, \{Victoria A\} and Christine Hirschberger and Marina Marcet-Houben and Dina Navon and Ali Andrescavage and Ksenia Skvortsova and Duckett, \{Paul Edward\} and {\'A}lvaro Gonz{\'a}lez-Rajal and Ozren Bogdanovic and Gibcus, \{Johan H\} and Liyan Yang and Lourdes Gallardo-Fuentes and Ismael Sospedra and Javier Lopez-Rios and Fabrice Darbellay and Axel Visel and Job Dekker and Neil Shubin and Toni Gabald{\'o}n and Tetsuya Nakamura and Tena, \{Juan J\} and Lupi{\'a}{\~n}ez, \{Dar{\'i}o G\} and Rokhsar, \{Daniel S\} and G{\'o}mez-Skarmeta, \{Jos{\'e} Luis\}",

note = "Acknowledgements We thank R. Schneider, D. Sherwood and the staff of the Marine Biological Laboratory Embryology course for providing laboratory space; L. Bertrand and the staff at Leica Microsystems for microscopy support; D. Remsen, S. Bennett, D. Calzarette, and the staff of the Marine Biological Laboratory and MBL Marine Resources Center for technical and animal husbandry assistance; A. Gillis for support and advice with RNA-seq and skate functional experiments; and A. Shindo for technical support of image analysis. ",

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AU - de la Calle-Mustienes, Elisa

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AU - Paliou, Christina

AU - Naranjo, Silvia

AU - Martínez-García, Pedro Manuel

AU - Cases, Ildefonso

AU - Sleight, Victoria A

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AU - Navon, Dina

AU - Andrescavage, Ali

AU - Skvortsova, Ksenia

AU - Duckett, Paul Edward

AU - González-Rajal, Álvaro

AU - Bogdanovic, Ozren

AU - Gibcus, Johan H

AU - Yang, Liyan

AU - Gallardo-Fuentes, Lourdes

AU - Sospedra, Ismael

AU - Lopez-Rios, Javier

AU - Darbellay, Fabrice

AU - Visel, Axel

AU - Dekker, Job

AU - Shubin, Neil

AU - Gabaldón, Toni

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AU - Tena, Juan J

AU - Lupiáñez, Darío G

AU - Rokhsar, Daniel S

AU - Gómez-Skarmeta, José Luis

N1 - Acknowledgements We thank R. Schneider, D. Sherwood and the staff of the Marine Biological Laboratory Embryology course for providing laboratory space; L. Bertrand and the staff at Leica Microsystems for microscopy support; D. Remsen, S. Bennett, D. Calzarette, and the staff of the Marine Biological Laboratory and MBL Marine Resources Center for technical and animal husbandry assistance; A. Gillis for support and advice with RNA-seq and skate functional experiments; and A. Shindo for technical support of image analysis.

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N2 - Skates are cartilaginous fish whose body plan features enlarged wing-like pectoral fins, enabling them to thrive in benthic environments 1,2. However, the molecular underpinnings of this unique trait remain unclear. Here we investigate the origin of this phenotypic innovation by developing the little skate Leucoraja erinacea as a genomically enabled model. Analysis of a high-quality chromosome-scale genome sequence for the little skate shows that it preserves many ancestral jawed vertebrate features compared with other sequenced genomes, including numerous ancient microchromosomes. Combining genome comparisons with extensive regulatory datasets in developing fins-including gene expression, chromatin occupancy and three-dimensional conformation-we find skate-specific genomic rearrangements that alter the three-dimensional regulatory landscape of genes that are involved in the planar cell polarity pathway. Functional inhibition of planar cell polarity signalling resulted in a reduction in anterior fin size, confirming that this pathway is a major contributor to batoid fin morphology. We also identified a fin-specific enhancer that interacts with several hoxa genes, consistent with the redeployment of hox gene expression in anterior pectoral fins, and confirmed its potential to activate transcription in the anterior fin using zebrafish reporter assays. Our findings underscore the central role of genome reorganization and regulatory variation in the evolution of phenotypes, shedding light on the molecular origin of an enigmatic trait.

AB - Skates are cartilaginous fish whose body plan features enlarged wing-like pectoral fins, enabling them to thrive in benthic environments 1,2. However, the molecular underpinnings of this unique trait remain unclear. Here we investigate the origin of this phenotypic innovation by developing the little skate Leucoraja erinacea as a genomically enabled model. Analysis of a high-quality chromosome-scale genome sequence for the little skate shows that it preserves many ancestral jawed vertebrate features compared with other sequenced genomes, including numerous ancient microchromosomes. Combining genome comparisons with extensive regulatory datasets in developing fins-including gene expression, chromatin occupancy and three-dimensional conformation-we find skate-specific genomic rearrangements that alter the three-dimensional regulatory landscape of genes that are involved in the planar cell polarity pathway. Functional inhibition of planar cell polarity signalling resulted in a reduction in anterior fin size, confirming that this pathway is a major contributor to batoid fin morphology. We also identified a fin-specific enhancer that interacts with several hoxa genes, consistent with the redeployment of hox gene expression in anterior pectoral fins, and confirmed its potential to activate transcription in the anterior fin using zebrafish reporter assays. Our findings underscore the central role of genome reorganization and regulatory variation in the evolution of phenotypes, shedding light on the molecular origin of an enigmatic trait.

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KW - evoltionary development biology

KW - evolutionary genetics

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SP - 495

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JO - Nature

JF - Nature

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The little skate genome and the evolutionary emergence of wing-like fins

Abstract

Bibliographical note

Data Availability Statement

Funding

Keywords

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