Primate-specific retrotransposons and the evolution of circadian networks in the human brain

Neurosci Biobehav Rev. 2021 Dec;131:988-1004. doi: 10.1016/j.neubiorev.2021.09.049. Epub 2021 Sep 28.


The circadian rhythm of the human brain is attuned to sleep-wake cycles that entail global alterations in neuronal excitability. This periodicity involves a highly coordinated regulation of gene expression. A growing number of studies are documenting a fascinating connection between primate-specific retrotransposons (Alu elements) and key epigenetic regulatory processes in the primate brain. Collectively, these studies indicate that Alu elements embedded in the human neuronal genome mediate post-transcriptional processes that unite human-specific neuroepigenetic landscapes and circadian rhythm. Here, we review evidence linking Alu retrotransposon-mediated posttranscriptional pathways to circadian gene expression. We hypothesize that Alu retrotransposons participate in the organization of circadian brain function through multidimensional neuroepigenetic pathways. We anticipate that these pathways are closely tied to the evolution of human cognition and their perturbation contributes to the manifestation of human-specific neurological diseases. Finally, we address current challenges and accompanying opportunities in studying primate- and human-specific transposable elements.

Keywords: Alu elements; Cognition; Neuroepigenetics; Paraspeckle; Post-transcriptional regulation; SINE; Sleep.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alu Elements / genetics
  • Animals
  • Brain
  • Humans
  • Nervous System Diseases*
  • Primates / genetics
  • Retroelements* / genetics


  • Retroelements