Evolution and dysfunction of human cognitive and social traits: A transcriptional regulation perspective

Roman Zug, Tobias Uller

Research output: Contribution to journalReview articlepeer-review


Evolutionary changes in brain and craniofacial development have endowed humans with unique cognitive and social skills, but also predisposed us to debilitating disorders in which these traits are disrupted. What are the developmental genetic underpinnings that connect the adaptive evolution of our cognition and sociality with the persistence of mental disorders with severe negative fitness effects? We argue that loss of function of genes involved in transcriptional regulation represents a crucial link between the evolution and dysfunction of human cognitive and social traits. The argument is based on the haploinsufficiency of many transcriptional regulator genes, which makes them particularly sensitive to loss-of-function mutations. We discuss how human brain and craniofacial traits evolved through partial loss of function (i.e. reduced expression) of these genes, a perspective compatible with the idea of human self-domestication. Moreover, we explain why selection against loss-of-function variants supports the view that mutation-selection-drift, rather than balancing selection, underlies the persistence of psychiatric disorders. Finally, we discuss testable predictions.

Original languageEnglish
Article numbere43
JournalEvolutionary Human Sciences
Publication statusPublished - 2022 Sept 26

Subject classification (UKÄ)

  • Evolutionary Biology

Free keywords

  • haploinsufficiency
  • human self-domestication
  • loss of function
  • neurodevelopmental disorders
  • transcriptional regulation


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