生物谷报道：遗传学家进行的一项最新研究表明，人类精神分裂症致病基因很可能赋予携带者某些优势，从而受到自然选择的青睐，并在人类中长期存在下来。相关论文将发表在近期的《英国皇家学会会报B》（Proceedings of the Royal Society B）上。
领导该项研究的是加拿大Simon Fraser大学的Bernard Crespi，他和同事检验了人类与精神分裂症相关的76个DNA序列，并将它们与黑猩猩和短尾猿等灵长类动物以及小鼠、大鼠、牛和狗的基因进行了对比研究。
结果表明，76个基因中有28个表现出了受到进化青睐的痕迹——它们发生的变异比基因组中其他控制序列的更少，而且在有性生殖过程中，没有表现出明显的基因随机混合。这些证据表明，人类这些与精神分裂症有关的基因序列可能赋予了携带者一种进化优势。
实际上，一些遗传疾病在带给人们痛苦的同时，也让他们在某些方面获益。比如，导致胰腺囊肿性纤维化的基因变异可以预防霍乱，而形成镰状细胞的变异也可以使机体对疟疾免疫。不过由于影响精神分裂症的遗传基因很可能有数百个，而且存在地域性的差异，科学家对它们的具体作用还没有清晰的认识，因此，此次的遗传研究并没有确定精神分裂症赋予的优势到底是什么。
参与研究的英国Bath大学的Steve Dorus表示，“这是一个大问题，我们还没有很好的答案。”尽管如此，该结论还是可以解释为什么带给人类错觉、幻想和偏执倾向的精神分裂症能够在漫长的进化过程中遗传下来，而没有被自然的力量所淘汰。
一种可能的解释是患有精神分裂症的人会更加有创造性和想象能力，他们更善于解决生存问题并且找到伴侣。不过，Dorus强调，“现在就下确定的结论为时尚早，从严格的遗传学立场而言，精神分裂症与创造性之间的联系还不可靠。”（科学网 任霄鹏/编译）
原始出处:
Proceedings of the Royal Society B
10.1098/rspb.2007.0876
2007年9月4日
Adaptive evolution of genes underlying schizophrenia
Bernard Crespi1, Kyle Summers2, Steve Dorus3
1Department of Biosciences, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6
2Department of Biology, East Carolina University, Greenville, NC 27858-4353, USA
3Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
摘要
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.
Keywords
adaptive evolution, schizophrenia, positive Darwinian selection, disease genetics
References
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