Comparative single-cell transcriptomic analysis of primate brains highlights human-specific regulatory evolution

Area of Science:

• Neuroscience
• Evolutionary Biology
• Genomics

Background:

• Human cognitive function is linked to cortical expansion and cellular diversity.
• Mechanisms driving these innovations are poorly understood due to limited primate cellular data.

Purpose of the Study:

• To identify homologous cell types and gene co-expression networks in primate brains.
• To compare gene expression differences between human and non-human primates.
• To investigate the evolutionary significance of these expression changes.

Main Methods:

• Single-cell expression data from the middle temporal gyrus of five primate species (human, chimp, gorilla, macaque, marmoset).
• Identification of 57 homologous cell types and construction of cell type-specific gene co-expression networks.
• Comparative analysis of orthologue expression patterns and network connectivity across species.

Main Results:

• Generally conserved orthologue expression, but 24% of genes show extensive differences between humans and non-human primates, linked to brain disorders.
• A subset of genes exhibits deeply conserved co-expression in non-human animals but divergent relationships in humans (139 genes).
• Genes with human-specific expression profiles evolve under relaxed selection, potentially driving rapid brain evolution.

Conclusions:

• Significant gene expression divergence in the human brain compared to non-human primates.
• Specific genes with human-specific co-expression profiles may underlie unique cognitive abilities.
• These findings offer insights into the genetic basis of human brain evolution and associated disorders.