Accelerated evolution of oligodendrocytes in the human brain

Stefano Berto, Isabel Mendizabal, Noriyoshi Usui, Kazuya Toriumi, Paramita Chatterjee, Connor Douglas, Carol A. Tamminga, Todd M. Preuss, Soojin V. Yi, Genevieve Konopka

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Recent discussions of human brain evolution have largely focused on increased neuron numbers and changes in their connectivity and expression. However, it is increasingly appreciated that oligodendrocytes play important roles in cognitive function and disease. Whether both cell types follow similar or distinctive evolutionary trajectories is not known. We examined the transcriptomes of neurons and oligodendrocytes in the frontal cortex of humans, chimpanzees, and rhesus macaques. We identified human-specific trajectories of gene expression in neurons and oligodendrocytes and show that both cell types exhibit human-specific up-regulation. Moreover, oligodendrocytes have undergone more pronounced accelerated gene expression evolution in the human lineage compared to neurons. We highlighted human-specific coexpression networks with specific functions. Our data suggest that oligodendrocyte human-specific networks are enriched for alternative splicing and transcriptional regulation. Oligodendrocyte networks are also enriched for variants associated with schizophrenia and other neuropsychiatric disorders. Such enrichments were not found in neuronal networks. These results offer a glimpse into the molecular mechanisms of oligodendrocytes during evolution and how such mechanisms are associated with neuropsychiatric disorders.

Original languageEnglish (US)
Pages (from-to)24334-24342
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number48
DOIs
StatePublished - Nov 26 2019

Keywords

  • Brain evolution
  • Cell-type expression
  • Comparative primate genomics
  • Neurogenomics

ASJC Scopus subject areas

  • General

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