| RRC ID |
78675
|
| 著者 |
Agata A, Ohtsuka S, Noji R, Gotoh H, Ono K, Nomura T.
|
| タイトル |
A Neanderthal/Denisovan GLI3 variant contributes to anatomical variations in mice.
|
| ジャーナル |
Front Cell Dev Biol
|
| 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.
|
| 巻・号 |
11
|
| ページ |
1247361
|
| 公開日 |
2023-1-1
|
| DOI |
10.3389/fcell.2023.1247361
|
| PII |
1247361
|
| PMID |
38020913
|
| PMC |
PMC10651735
|
| リソース情報 |
| ヒト・動物細胞 |
293T(RCB2202) |
