Piebaldism and chromatophore development in reptiles are linked to the tfec gene

Reptiles display great diversity in color and pattern, yet much of what we know about vertebrate coloration comes from classic model species such as the mouse and zebrafish.1,2,3,4 Captive-bred ball pythons (Python regius) exhibit a remarkable degree of color and pattern variation. Despite the wide...

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Published inCurrent biology Vol. 33; no. 4; pp. 755 - 763.e3
Main Authors Garcia-Elfring, Alan, Sabin, Christina E., Iouchmanov, Anna L., Roffey, Heather L., Samudra, Sukhada P., Alcala, Aaron J., Osman, Rida S., Lauderdale, James D., Hendry, Andrew P., Menke, Douglas B., Barrett, Rowan D.H.
Format Journal Article
LanguageEnglish
Published England Elsevier Inc 27.02.2023
Subjects
Animals
ball python
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Chromatophores
color morph
genomics
Lizards - genetics
Mendelian phenotype
Mice
Piebaldism
pigmentation
Pigmentation - genetics
Zebrafish
Zebrafish Proteins
pigmentation
genomics
color morph
Mendelian phenotype
ball python
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Summary:Reptiles display great diversity in color and pattern, yet much of what we know about vertebrate coloration comes from classic model species such as the mouse and zebrafish.1,2,3,4 Captive-bred ball pythons (Python regius) exhibit a remarkable degree of color and pattern variation. Despite the wide range of Mendelian color phenotypes available in the pet trade, ball pythons remain an overlooked species in pigmentation research. Here, we investigate the genetic basis of the recessive piebald phenotype, a pattern defect characterized by patches of unpigmented skin (leucoderma). We performed whole-genome sequencing and used a case-control approach to discover a nonsense mutation in the gene encoding the transcription factor tfec, implicating this gene in the leucodermic patches in ball pythons. We functionally validated tfec in a lizard model (Anolis sagrei) using the gene editing CRISPR/Cas9 system and TEM imaging of skin. Our findings show that reading frame mutations in tfec affect coloration and lead to a loss of iridophores in Anolis, indicating that tfec is required for chromatophore development. This study highlights the value of captive-bred ball pythons as a model species for accelerating discoveries on the genetic basis of vertebrate coloration. •Captive-bred ball pythons show extensive Mendelian variation in pigmentation•The recessive piebald phenotype is linked to a premature stop codon in tfec•Mutated tfec inhibits development of iridophores in a lizard model Garcia-Elfring et al. use population genetics, gene editing, and TEM imaging to show that a transcription factor is linked to white spotting in ball pythons and iridophore development in a lizard model.
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A.G.-E., A.P.H., and R.D.H.B. conceived the study and its design, with contributions from J.D.L. and D.B.M. H.L.R. collected and catalogued shed skin samples. A.G.-E. performed DNA extractions and bioinformatics to analyze whole-genome data. D.B.M. and J.D.L. carried out CRISPR/Cas9 project oversight. C.E.S. performed in vitro test of tfec CRISPR gRNA, preparation of tfec RNP, tfec surgeries and microinjection, breeding of tfec−/− lizards, eye and skin dissections, stereomicroscope images, preparation of skin samples for TEM imaging, and working with the TEM microscopy technician. A.L.I. performed egg collection, egg care, screening hatchlings for phenotypes, documentation, and initial analysis of tfec phenotypes, genotyping, raising hatchlings, and breeding tfec−/− lizards. S.P.S. performed tfec surgeries and microinjections. A.J.A. documented tfec phenotypes. R.S.O. was instrumental in the creation of the tyrosinase mutant line. J.D.L. contributed to the analysis of tfec phenotypes, project oversight, and project funding (NSF EDGE grant). D.B.M. performed tfec gene annotation, gRNA design, genotyping design, analysis of tfec phenotypes, project oversight, and project funding (NSF EDGE grant). A.G.-E. wrote the original draft with all authors contributing to review and editing.
AUTHOR CONTRIBUTIONS
ISSN:0960-9822
1879-0445
DOI:10.1016/j.cub.2023.01.004