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Adaptive evolution of genes underlying schizophrenia
Bernard Crespi1, Kyle Summers, Steve Dorus
1Department of Biosciences, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6. crespi@sfu.ca
Proceedings. Biological Sciences
|September 6, 2007
Summary
Genetic factors contributing to schizophrenia may have been positively selected during human evolution. This suggests schizophrenia could be a byproduct of adaptive cognitive trait evolution.
Area of Science:
- Evolutionary genetics
- Neuroscience
- Human evolution
Background:
- Schizophrenia presents an evolutionary paradox due to its high heritability and negative fitness effects, yet it persists globally.
- A recent hypothesis suggests schizophrenia liability arose as a byproduct of selection for enhanced human cognitive abilities.
Purpose of the Study:
- To test the hypothesis that genes increasing schizophrenia risk have undergone positive selection in human and primate evolution.
- To investigate evolutionary pressures on genes associated with schizophrenia.
Main Methods:
- Analysis of recent selective sweeps in human populations.
- Maximum-likelihood tests for selection across primate evolution.
- Comparative analysis of schizophrenia-associated genes against neuronal control genes using HapMap and PAML.
Main Results:
- Significant evidence of positive selection was found for 28 out of 76 genes linked to schizophrenia liability.
- Genes like DISC1, DTNBP1, and NRG1 showed strong signals of positive selection.
- DISC1 exhibited accelerated evolution, particularly in its coding exon 2.
- Schizophrenia-associated genes were significantly enriched for positive selection signals compared to neuronal control genes.
Conclusions:
- The findings provide convergent evidence supporting the hypothesis that schizophrenia is partly a byproduct of adaptive evolutionary changes in human cognition.
- While the exact selective forces are unknown, the study indicates a link between cognitive evolution and schizophrenia risk genes.
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