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Area of Science:

  • Genomics
  • Evolutionary Biology
  • Neuroscience

Background:

  • Gene regulatory elements are crucial for human-specific traits like cortical expansion.
  • The mutational processes shaping these elements and their target genes remain unclear.
  • Human Ancestor Quickly Evolved Regions (HAQERs) represent fast-evolving genomic areas.

Purpose of the Study:

  • Investigate the regulatory function and evolutionary origins of HAQERs.
  • Understand their role in human cerebral cortex development.
  • Identify target genes influenced by HAQERs.

Main Methods:

  • Identified 50 HAQERs with accessible chromatin in developing human cortex.
  • Utilized CRISPRi lentiviral vectors to link HAQERs to target genes.
  • Analyzed CpG gains and human-specific epigenomic marks.

Main Results:

  • Discovered 107 HAQERs with significant CpG gains, termed HAQER CpG Beacons.
  • Found evidence for GC-biased gene conversion (gBGC) and selection in HAQER evolution.
  • Identified HAQER CpG Beacons linked to genes implicated in neurological disorders (CHL1, DPP10).

Conclusions:

  • HAQERs and their target genes are revealed.
  • A model suggests gBGC and selection drive fixation of regulatory CpG variants.
  • This process contributes to regulatory innovations in the human cortex.