NOVA1, a neuron-specific RNA binding protein & splicing factor, likely impacted language function in human evolution. Human NOVA1 is unique (vs mammals, Neanderthals), & it changes vocalization in CRISPR’d mice!
TY @NatureComms @RockefellerUniv team, collaborators @erichjarvis @asiepel labs
🧵👇
TY @NatureComms @RockefellerUniv team, collaborators @erichjarvis @asiepel labs
🧵👇
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In our study (below), we used CRISPR to make humanized NOVA1 in mice, to explore its role in RNA regulation, neural function, and vocalization.
Here’s what we found. 🧵👇 #RNA #evolution #language
https://www.nature.com/articles/s41467-025-56579-2
FOXP2 is one “language gene,” but doesn't have a unique role in human-specific speech evolution. Enter NOVA1, a neuron-specific RNA-binding protein with a human-specific amino acid substitution. 🧠🔬
Why? This amino acid change is fixed in modern humans, but absent in Neanderthals & Denisovans—a sign of ancient evolutionary selection. 🧬🦴
🔹 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.