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

Hamsini Suresh1, Megan Crow2, Nikolas Jorstad3

  • 1Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.

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Summary

Human brain evolution involves unique gene expression changes. A study comparing primate brains found specific gene networks in humans may drive cognitive advancements and are linked to brain disorders.

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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.