A Neanderthal/Denisovan GLI3 variant contributes to anatomical variations in mice.
Front Cell Dev Biol
; 11: 1247361, 2023.
Article
en En
| MEDLINE
| ID: mdl-38020913
ABSTRACT
Changes in genomic structures underlie phenotypic diversification in organisms. Amino acid-changing mutations affect pleiotropic functions of proteins, although little is known about how mutated proteins are adapted in existing developmental programs. Here we investigate the biological effects of a variant of the GLI3 transcription factor (GLI3R1537C) carried in Neanderthals and Denisovans, which are extinct hominins close to modern humans. R1537C does not compromise protein stability or GLI3 activator-dependent transcriptional activities. In contrast, R1537C affects the regulation of downstream target genes associated with developmental processes. Furthermore, genome-edited mice carrying the Neanderthal/Denisovan GLI3 mutation exhibited various alterations in skeletal morphology. Our data suggest that an extinct hominin-type GLI3 contributes to species-specific anatomical variations, which were tolerated by relaxed constraint in developmental programs during human evolution.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Front Cell Dev Biol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
CH
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SUIZA
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SUÍÇA
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SWITZERLAND