Tracing the evolutionary history of human neocortical regulation.

Comparative multi-omics across nine mammals and zebrafish links regulatory elements with distinct evolutionary histories to predicted enhancer–gene relationships affecting brain function and disease risk.

• Why it matters: Regulatory DNA’s evolutionary origins are unclear, limiting how we interpret brain function and disease risk from comparative genomics and multi-omics.
• What they did: They integrated sequence conservation with predicted enhancer–gene links across nine mammals and zebrafish, then tested key regulatory relationships using functional assays.
• The result: The work shows how regulatory elements with different evolutionary histories contribute to brain function and helps connect evolutionary regulation to disease risk.

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