生物谷報(bào)道：遺傳學(xué)家進(jìn)行的一項(xiàng)最新研究表明,，人類精神分裂癥致病基因很可能賦予攜帶者某些優(yōu)勢(shì)，從而受到自然選擇的青睞,，并在人類中長(zhǎng)期存在下來,。相關(guān)論文將發(fā)表在近期的《英國(guó)皇家學(xué)會(huì)會(huì)報(bào)B》（Proceedings of the Royal Society B）上。
領(lǐng)導(dǎo)該項(xiàng)研究的是加拿大Simon Fraser大學(xué)的Bernard Crespi,，他和同事檢驗(yàn)了人類與精神分裂癥相關(guān)的76個(gè)DNA序列,，并將它們與黑猩猩和短尾猿等靈長(zhǎng)類動(dòng)物以及小鼠、大鼠,、牛和狗的基因進(jìn)行了對(duì)比研究,。
結(jié)果表明，76個(gè)基因中有28個(gè)表現(xiàn)出了受到進(jìn)化青睞的痕跡——它們發(fā)生的變異比基因組中其他控制序列的更少,，而且在有性生殖過程中,，沒有表現(xiàn)出明顯的基因隨機(jī)混合。這些證據(jù)表明,，人類這些與精神分裂癥有關(guān)的基因序列可能賦予了攜帶者一種進(jìn)化優(yōu)勢(shì),。
實(shí)際上，一些遺傳疾病在帶給人們痛苦的同時(shí),，也讓他們?cè)谀承┓矫娅@益,。比如，導(dǎo)致胰腺囊腫性纖維化的基因變異可以預(yù)防霍亂,，而形成鐮狀細(xì)胞的變異也可以使機(jī)體對(duì)瘧疾免疫,。不過由于影響精神分裂癥的遺傳基因很可能有數(shù)百個(gè)，而且存在地域性的差異,，科學(xué)家對(duì)它們的具體作用還沒有清晰的認(rèn)識(shí),，因此，此次的遺傳研究并沒有確定精神分裂癥賦予的優(yōu)勢(shì)到底是什么,。
參與研究的英國(guó)Bath大學(xué)的Steve Dorus表示,，“這是一個(gè)大問題，我們還沒有很好的答案。”盡管如此,，該結(jié)論還是可以解釋為什么帶給人類錯(cuò)覺,、幻想和偏執(zhí)傾向的精神分裂癥能夠在漫長(zhǎng)的進(jìn)化過程中遺傳下來，而沒有被自然的力量所淘汰,。
一種可能的解釋是患有精神分裂癥的人會(huì)更加有創(chuàng)造性和想象能力,，他們更善于解決生存問題并且找到伴侶。不過,，Dorus強(qiáng)調(diào),，“現(xiàn)在就下確定的結(jié)論為時(shí)尚早，從嚴(yán)格的遺傳學(xué)立場(chǎng)而言,，精神分裂癥與創(chuàng)造性之間的聯(lián)系還不可靠。”（科學(xué)網(wǎng) 任霄鵬/編譯）
原始出處:
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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