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Research Article

Genome mapping of a LYST mutation in corn snakes indicates that vertebrate chromatophore vesicles are lysosome-related organelles

View ORCID ProfileAsier Ullate-Agote, Ingrid Burgelin, Adrien Debry, Carine Langrez, Florent Montange, View ORCID ProfileRodrigue Peraldi, View ORCID ProfileJean Daraspe, View ORCID ProfileHenrik Kaessmann, View ORCID ProfileMichel C. Milinkovitch, and View ORCID ProfileAthanasia C. Tzika
PNAS October 20, 2020 117 (42) 26307-26317; first published October 5, 2020; https://doi.org/10.1073/pnas.2003724117
Asier Ullate-Agote
aLaboratory of Artificial & Natural Evolution (LANE), Department of Genetics & Evolution, University of Geneva, CH-1211 Geneva, Switzerland;
bSIB Swiss Institute of Bioinformatics, Switzerland;
cInstitute of Genetics and Genomics of Geneva (iGE3), University of Geneva, Geneva, Switzerland;
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  • ORCID record for Asier Ullate-Agote
Ingrid Burgelin
aLaboratory of Artificial & Natural Evolution (LANE), Department of Genetics & Evolution, University of Geneva, CH-1211 Geneva, Switzerland;
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Adrien Debry
aLaboratory of Artificial & Natural Evolution (LANE), Department of Genetics & Evolution, University of Geneva, CH-1211 Geneva, Switzerland;
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Carine Langrez
aLaboratory of Artificial & Natural Evolution (LANE), Department of Genetics & Evolution, University of Geneva, CH-1211 Geneva, Switzerland;
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Florent Montange
aLaboratory of Artificial & Natural Evolution (LANE), Department of Genetics & Evolution, University of Geneva, CH-1211 Geneva, Switzerland;
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Rodrigue Peraldi
aLaboratory of Artificial & Natural Evolution (LANE), Department of Genetics & Evolution, University of Geneva, CH-1211 Geneva, Switzerland;
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  • ORCID record for Rodrigue Peraldi
Jean Daraspe
dFaculté de Biologie et de Médecine, Electron Microscopy Facility, University of Lausanne, CH-1015 Lausanne, Switzerland;
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  • ORCID record for Jean Daraspe
Henrik Kaessmann
eDKFZ-ZMBH Alliance, Center for Molecular Biology of Heidelberg University (ZMBH), D-69120 Heidelberg, Germany
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  • ORCID record for Henrik Kaessmann
Michel C. Milinkovitch
aLaboratory of Artificial & Natural Evolution (LANE), Department of Genetics & Evolution, University of Geneva, CH-1211 Geneva, Switzerland;
bSIB Swiss Institute of Bioinformatics, Switzerland;
cInstitute of Genetics and Genomics of Geneva (iGE3), University of Geneva, Geneva, Switzerland;
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  • ORCID record for Michel C. Milinkovitch
Athanasia C. Tzika
aLaboratory of Artificial & Natural Evolution (LANE), Department of Genetics & Evolution, University of Geneva, CH-1211 Geneva, Switzerland;
bSIB Swiss Institute of Bioinformatics, Switzerland;
cInstitute of Genetics and Genomics of Geneva (iGE3), University of Geneva, Geneva, Switzerland;
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  • ORCID record for Athanasia C. Tzika
  • For correspondence: athanasia.tzika@unige.ch
  1. Edited by Günter P. Wagner, Yale University, New Haven, CT, and approved September 3, 2020 (received for review February 27, 2020)

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    Fig. 1.

    Coloration of (A) wild type and (B) lavender corn snakes. A dorsal overview (Left), close-ups of lateral and ventral views (Center), and a head dorsal view (Right) are provided. The insets show the iris coloration. The coloration of lavender individuals is heavily affected, but no obvious change in the color pattern is detectable.

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    Fig. 2.

    BUSCO results for the corn snake genome sequenced and assembled here as well as for four previously published squamate genomes. The genome completeness assessment was performed using the 3,950 single-copy genes of the Tetrapoda set.

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    Fig. 3.

    Mapping the lavender variant. (A) Proportion (y axis) of quality-filtered SNP/MNP cosegregating with the lavender locus in the four genome libraries compared to informative quality-filtered parental variants (homozygous in the lavender/lavender father and heterozygous in the lavender/+ female). Proportions are calculated for scaffolds >1 Mb, with a 1-Mb sliding window and a step of 100 kb. Scaffolds (alternatingly colored black and red) are ordered from longest to shortest, and the two superscaffolds containing the lavender interval are indicated. A close-up of these superscaffolds is provided in SI Appendix, Fig. S7. (B) Number of biallelic variants (SNP/MNP and indels) in 500-kb intervals cosegregating with the lavender locus in superscaffolds 423 and 108 based on the family mapping. (C) Number of biallelic variants (SNP/MNP and indels) in 500-kb intervals cosegregating with the lavender locus in superscaffolds 423 and 108 based on the extended mapping. (B and C) Scaffolds are ordered and oriented based on their synteny to the G. gallus and A. carolinensis genomes. Dark green and dark red bins correspond to the 25.3-Mb region with the highest proportion of cosegregating variants in the family mapping. The length/position of the two intervals is shown with a thick line under each graph, and an arrow points to the position of LYST.

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    Fig. 4.

    Wild type and lavender corn snake chromatophores of 1- and 3-year-old animals. In the wild type: (A and K) epidermal melanocytes, (B and L) dermal melanocytes with ellipsoidal mature melanosomes (a few are at earlier stages of maturation at 1 y old), (C and M) xanthophores with xanthosomes containing concentric lamellae (at 1 y old, some xanthosomes are at earlier stages of maturation and contain amorphous material), and (D and N) ventral and (E and O) dorsal iridophores carrying crystals of guanine. In the lavender: (F and P) epidermal melanosomes are larger than in the wild type and have irregular shapes; (G and Q) dermal melanosomes are larger and more irregularly shaped than in the wild type and mature more slowly, as several are not fully melanized after 1 y, and become bigger and irregularly shaped; (H and R) the amorphous material of the xanthosomes accumulates more slowly and forms irregularly shaped lamellae in the lavender instead of concentric ones as in the wild type; and (I and S) ventral and (J and T) dorsal guanine crystals in iridophores are more irregularly shaped and might accumulate in larger compartments than in the wild type. (Scale bars, 1 μm.)

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    Fig. 5.

    LAMP1 immunostaining of liver cells. (A) Lysosomes of the wild type corn snake are small and widely distributed in the hepatocytes, whereas (B) lysosomes of the lavender corn snake aggregate and form bigger structures. Dashed squares include the regions shown in greater magnification below. (Green: LAMP1, blue: nuclear DAPI staining; scale bars, 10 μm.)

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    Table 1.

    Statistics for the final corn snake genome assembly compared to other published snake genomes

    SpeciesAssembly length in Gb (% of gaps)Number of sequencesN50, kbL50
    P. guttatus (this article)1.71 (4.7%)34,26816,79024
    Boa constrictor1.44 (3.9%)19,9274,50590
    Python bivittatus1.44 (3.5%)39,1132141,939
    Deinagkistrodon acutus1.51 (5.9%)162,5712,075199
    Pseudonaja textilis1.59 (2.5%)28,55014,68631
    Notechis scutatus1.67 (4.8%)52,4145,99766
    Crotalus viridis1.34 (6.2%)7,043103,2913

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Genome mapping of a LYST mutation in corn snakes indicates that vertebrate chromatophore vesicles are lysosome-related organelles
Asier Ullate-Agote, Ingrid Burgelin, Adrien Debry, Carine Langrez, Florent Montange, Rodrigue Peraldi, Jean Daraspe, Henrik Kaessmann, Michel C. Milinkovitch, Athanasia C. Tzika
Proceedings of the National Academy of Sciences Oct 2020, 117 (42) 26307-26317; DOI: 10.1073/pnas.2003724117

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Genome mapping of a LYST mutation in corn snakes indicates that vertebrate chromatophore vesicles are lysosome-related organelles
Asier Ullate-Agote, Ingrid Burgelin, Adrien Debry, Carine Langrez, Florent Montange, Rodrigue Peraldi, Jean Daraspe, Henrik Kaessmann, Michel C. Milinkovitch, Athanasia C. Tzika
Proceedings of the National Academy of Sciences Oct 2020, 117 (42) 26307-26317; DOI: 10.1073/pnas.2003724117
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