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A functional MiR-124 binding-site polymorphism in IQGAP1 affects human cognitive performance.

Lixin Yang1, Rui Zhang2, Ming Li1

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Genetic variations impact human cognitive performance. A specific SNP (rs1042538) in the IQGAP1 gene influences brain expression and tactile abilities, particularly in males, suggesting recent natural selection on cognitive traits.

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Area of Science:

  • Human evolution
  • Neurogenetics
  • Cognitive science

Background:

  • Human cognitive performance is a heritable trait influenced by brain evolution.
  • Genes undergoing adaptive evolution with significant effects on cognition remain largely unidentified.
  • IQ motif containing GTPase activating protein 1 (IQGAP1) is a scaffold protein crucial for learning and memory.

Purpose of the Study:

  • To investigate the role of a specific single nucleotide polymorphism (SNP), rs1042538, in the IQGAP1 gene.
  • To determine if this SNP influences IQGAP1 expression and cognitive performance.
  • To explore the evolutionary history of this SNP in human populations.

Main Methods:

  • In vitro and in vivo experiments to assess the impact of rs1042538 on miR-124 targeting of IQGAP1.
  • Analysis of IQGAP1 expression levels in individuals with different rs1042538 alleles.
  • Examination of the association between rs1042538 and tactile performance in two independent human cohorts.
  • Population-level analysis of allele frequency distribution for rs1042538.

Main Results:

  • The SNP rs1042538 significantly influences the interaction between miR-124 and IQGAP1.
  • Individuals with the derived T allele exhibit higher IQGAP1 brain expression compared to ancestral A allele carriers.
  • A male-specific association was found between rs1042538 and enhanced tactile performance in two cohorts.
  • rs1042538 shows a highly diverged allele frequency distribution across global populations, indicative of natural selection or population expansion.

Conclusions:

  • Sequence variations affecting cognitive performance are present in modern human populations.
  • The rs1042538 SNP in IQGAP1 is a candidate for recent natural selection impacting cognitive abilities, specifically tactile performance in males.
  • This finding highlights the ongoing evolutionary influence on human cognitive traits.