| First Author | Agata A | Year | 2023 |
| Journal | Front Cell Dev Biol | Volume | 11 |
| Pages | 1247361 | PubMed ID | 38020913 |
| Mgi Jnum | J:343594 | Mgi Id | MGI:7562874 |
| Doi | 10.3389/fcell.2023.1247361 | Citation | Agata A, et al. (2023) A Neanderthal/Denisovan GLI3 variant contributes to anatomical variations in mice. Front Cell Dev Biol 11:1247361 |
| abstractText | 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 (GLI3(R1537C)) 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. |
