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April 15th, 2025
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Institute of Biosciences, University of Sao Paulo - Brazil
evolutionary biology
biorxiv

Rapid expansion of synaptic complexity as a key contributor to cognitive growth in early humans

Lepski, G.Open in Google Scholar•Arevalo, A.Open in Google Scholar•Silva de Camargo, P.Open in Google Scholar•Nunes, K.Open in Google Scholar•Barbosa Lemes, R.Open in Google Scholar•Ferraz, T.Open in Google Scholar•Strauss, A.Open in Google Scholar•Miyagawa, S.Open in Google Scholar

Primates have been evolving for over 50 million years. At some point, humans made an unusually large evolutionary leap, giving rise to abilities like the creation of tools, intricate art and complex language. The neuronal synapse, a key player in information processing and brain plasticity, has largely been ignored as a potential factor in this process. Here we used the genomic databases of ancestral hominins to compare the expression levels of 995 genes expressed in the human nervous system among archaic (6 Neanderthal, 2 Denisovan) and modern humans (62 African Modern Human). We searched in the 95th top p-value for variants whose derived alleles had a frequency >90% in modern and <10% in archaic humans. We then used the STRING database to perform protein-protein interaction networks on the 95th top p-value for the variants. We identified genetic variants in 15 genes, and in two (STX16 and UBASH3B), the allele frequency was significantly higher in modern versus archaic humans. These genes have previously been associated with critical cellular (proliferation, differentiation, migration, survival) and synaptic (exocytosis, synaptic vesicle fusion) processes, supporting the idea that changes in synaptic structure and function may have played a key role in the development of human cognition.

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