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PolyQ length-based molecular encoding of vocalization frequency in FOXP2

The transcription factor FOXP2, a regulator of vocalization- and speech/language-related phenotypes, contains two long polyQ repeats (Q(1) and Q(2)) displaying marked, still enigmatic length variation across mammals. We found that the Q(1)/Q(2) length ratio quantitatively encodes vocalization freque...

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Detalles Bibliográficos
Autores principales: Vaglietti, Serena, Villeri, Veronica, Dell’Oca, Marco, Marchetti, Chiara, Cesano, Federico, Rizzo, Francesca, Miller, Dave, LaPierre, Louis, Pelassa, Ilaria, Monje, Francisco J., Colnaghi, Luca, Ghirardi, Mirella, Fiumara, Ferdinando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10582585/
https://www.ncbi.nlm.nih.gov/pubmed/37860754
http://dx.doi.org/10.1016/j.isci.2023.108036
Descripción
Sumario:The transcription factor FOXP2, a regulator of vocalization- and speech/language-related phenotypes, contains two long polyQ repeats (Q(1) and Q(2)) displaying marked, still enigmatic length variation across mammals. We found that the Q(1)/Q(2) length ratio quantitatively encodes vocalization frequency ranges, from the infrasonic to the ultrasonic, displaying striking convergent evolution patterns. Thus, species emitting ultrasonic vocalizations converge with bats in having a low ratio, whereas species vocalizing in the low-frequency/infrasonic range converge with elephants and whales, which have higher ratios. Similar, taxon-specific patterns were observed for the FOXP2-related protein FOXP1. At the molecular level, we observed that the FOXP2 polyQ tracts form coiled coils, assembling into condensates and fibrils, and drive liquid-liquid phase separation (LLPS). By integrating evolutionary and molecular analyses, we found that polyQ length variation related to vocalization frequency impacts FOXP2 structure, LLPS, and transcriptional activity, thus defining a novel form of polyQ length-based molecular encoding of vocalization frequency.