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Published online: 5 September 2007; | doi:10.1038/news070903-6
'favoured by evolution'
Sequences linked to brain disorder
show hallmarks of natural selection.
by Michael Hopkin
The genes that underpin schizophrenia may have been favoured by natural selection, according to a survey of human and primate genetic sequences. The discovery suggests that genes linked to the debilitating brain condition conferred some advantage that allowed them to persist in the population -- although it is far from clear what this advantage might have been.
Researchers led by Bernard Crespi of Simon Fraser University in Burnaby, Canada, examined 76 DNA sequences linked to schizophrenia. They compared these human sequences with one another and with those of primates such as chimps and macaques, as well as with some from mice, rats, cows and dogs.
Of the 76 genes studied, 28 showed evidence of being favoured by natural selection. They showed less variation than other control sequences from elsewhere in the genome, and had less evidence of having been jumbled up by the random mixing of genes that occurs during sexual reproduction. These findings suggest that these schizophrenia-linked sequences may have conferred an evolutionary advantage, the researchers explain in Proceedings of the Royal Society B.
The genetic data provide no clues as to the kind of advantage that schizophrenia-linked genes might have offered. "That is the big question and we don't really have a good answer to that," admits Crespi's colleague Steve Dorus of the University of Bath, UK.
Nevertheless, the results might explain why schizophrenia -- which can be inherited and commonly involves delusions, hallucinations and paranoia -- has persisted without being stamped out by evolutionary forces. Although a severe psychotic illness, it is thought to affect as many as 1% of people at some point in their lives, worldwide.
Some inherited diseases also benefit the person affected, which helps to explain why they have persisted. The mutation that causes cystic fibrosis, for example, is known to protect carriers from cholera. And people who carry the mutation behind sickle-cell disease also inherit an immunity to malaria. But unpicking the advantage of schizophrenia will be difficult, as its genetics are poorly understood. It is probably underpinned by hundreds of genes, each with a tiny effect. Although some mutations increase susceptibility to schizophrenia, it is not known what else they might do. "The picture's not at all clear -- the genetics of schizophrenia has been a mess for twenty years," comments neuroscientist David St Clair of the University of Aberdeen, UK.
Psychiatric studies have suggested that people with schizophrenia could be more creative or imaginative than the general population, which raises the possibility that schizophrenia genes helped carriers to solve survival problems or attract a mate. It's too early to draw firm conclusions from this theory, however, says Dorus. "From a strict genetic standpoint, links between schizophrenia and creativity are still tenuous," he says. The problem, he adds, is that experts do not have a clear picture of how genes can specifically affect a creative streak.
The problem is compounded by the fact that so many genes are linked to the disease, and that they vary between populations around the world. Only four of the gene sequences identified by the researchers showed evidence of natural selection in more than one continent. This suggests that different genes may have been favoured in the evolution of different populations, even though schizophrenia is found throughout the world. It also suggests that these mutations were subject to natural selection after humankind embarked on its spread throughout the world over the past 60,000 years.
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