[evo.theory] Reading Group on Friday 12pm: Adaptive evolution of genes underlying schizophrenia

[Brett Calcott]

Hi all,

A change of pace this week. I came across this paper last week and a
few people seemed interested in it. We'll meet in the Bozo reading
room at 12pm.

Adaptive evolution of genes underlying schizophrenia
Bernard Crespi, Kyle Summers, Steve Dorus

Schizophrenia poses an evolutionary-genetic paradox because it
exhibits strongly negative fitness effects and high heritability, yet
it persists at a prevalence of approximately 1% across all human
cultures. Recent theory has proposed a resolution: that genetic
liability to schizophrenia has evolved as a secondary consequence of
selection for human cognitive traits. This hypothesis predicts that
genes increasing the risk of this disorder have been subject to
positive selection in the evolutionary history of humans and other
primates. We evaluated this prediction using tests for recent
selective sweeps in human populations and maximum-likelihood tests for
selection during primate evolution. Significant evidence for positive
selection was evident using one or both methods for 28 of 76 genes
demonstrated to mediate liability to schizophrenia, including DISC1,
DTNBP1 and NRG1, which exhibit especially strong and well-replicated
functional and genetic links to this disorder. Strong evidence of
non-neutral, accelerated evolution was found for DISC1, particularly
for exon 2, the only coding region within the schizophrenia-associated
haplotype. Additionally, genes associated with schizophrenia exhibited
a statistically significant enrichment in their signals of positive
selection in HapMap and PAML analyses of evolution along the human
lineage, when compared with a control set of genes involved in
neuronal activities. The selective forces underlying adaptive
evolution of these genes remain largely unknown, but these findings
provide convergent evidence consistent with the hypothesis that
schizophrenia represents, in part, a maladaptive by-product of
adaptive changes during human evolution.

-- 
Brett Calcott
Philosophy Program, Research School of Social Sciences, AND
Centre for Macroevolution & Macroecology, School of Botany & Zoology,
AUSTRALIAN NATIONAL UNIVERSITY,
Canberra, ACT, 0200, AUSTRALIA
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