To study NOVA1’s role, we used CRISPR to introduce the human-specific I197V mutation into mice (Nova1hu/hu).
Why? This amino acid change is fixed in modern humans, but absent in Neanderthals & Denisovans—a sign of ancient evolutionary selection. 🧬🦴
Why? This amino acid change is fixed in modern humans, but absent in Neanderthals & Denisovans—a sign of ancient evolutionary selection. 🧬🦴
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🔹 CLIP in hNOVA1 brain had different NOVA1 binding & splicing differences in neurons.
🔹 These RNAs affect synapses and behavior-related pathways.
🔹 Key brain regions involved in vocalization (e.g., cortex, midbrain (PAG)) showed altered NOVA1 binding.
🐭 hNOVA1 pups emitted altered calls when separated from their mothers.
🐭 Adult males had different vocalization patterns when producing courtship song to females.
The parallels to human speech evolution are striking.
We analyzed 650,058 human genomes and found near-fixation across all modern populations.
Our evolutionary modeling suggests strong evolutionary selection—one of the most significant sweeps in the human genome.
Our study provides the first direct evidence that an RNA-binding protein, not just a transcription factor like FOXP2, helped shape human communication. 🗣️
🔹 NOVA1 links RNA regulation to speech evolution.
🔹 Could similar mechanisms underlie neurodevelopmental disorders?
🔹 Further studies could help unravel genetic underpinnings of autism & speech-related conditions.
https://www.rockefeller.edu/our-scientists/heads-of-laboratories/952-robert-b-darnell/