來自加拿大多倫多大學(xué)細(xì)胞與生物分子研究Donnelly中心（Donnelly Center for Cellular and Biomolecular Research）,、美國加州大學(xué)洛杉磯分校分子生物學(xué)研究院、愛荷華州大學(xué)等處的研究人員揭示了為什么盡管人類與黑猩猩在基因上只存在大約1%的差異,，卻在行為,、思考和對抗疾病方面有很大的差異。這一研究成果公布在《基因與發(fā)育》（Genes and Development）雜志上,。
這一由多倫多大學(xué)細(xì)胞與生物分子中心主導(dǎo)完成的創(chuàng)新性研究比較了人類和黑猩猩大腦,，以及心臟組織的樣品，獲得了對于這些令人費解的謎的新解釋,，研究人員主要包括多倫多大學(xué)教授Benjamin Blencow,，以及其研究生John Calarco等人，他們共同努力發(fā)現(xiàn)了遺傳物質(zhì)在剪接翻譯成蛋白過程中的重要差異,。
Blencowe表示,，“顯然人類與黑猩猩在許多水平上差異極大，但是我們希望了解剪接過程是否在其中扮演了極為重要的角色，決定一些基礎(chǔ)性差異”,，“我們驚訝的發(fā)現(xiàn),，研究中的6-8%的可變剪接存在差異——這是十分大的差異，并且這些表現(xiàn)出剪接差異的基因都與許多重要的事件相關(guān),，比如某些疾病的易感性,。”
剪接是細(xì)胞生物體產(chǎn)生復(fù)雜蛋白的一個重要機制，指基因的編碼區(qū)域參與到蛋白產(chǎn)生的遺傳信息中來,，可變剪接能夠用相同的遺傳信息產(chǎn)生多種類型的蛋白,，這一新發(fā)現(xiàn)揭示可變剪接過程在人類和黑猩猩之間存在巨大差異。
Blencowe認(rèn)為,，這一研究也對于未來人類和黑猩猩疾病的治療意義重大,，“了解我們?yōu)槭裁慈绱瞬煌瑢τ诶斫鉃槭裁茨承┘膊≈挥绊懸粋€種群，而不影響另一個種群具有深遠(yuǎn)的意義,。”
原始出處:
Published online before print October 31, 2007, 10.1101/gad.1606907
GENES & DEVELOPMENT 21:2963-2975, 2007
Global analysis of alternative splicing differences between humans and chimpanzees
John A. Calarco1,2,8, Yi Xing3,4,8, Mario Cáceres5,6,8, Joseph P. Calarco1, Xinshu Xiao7, Qun Pan1, Christopher Lee3, Todd M. Preuss5,10, and Benjamin J. Blencowe1,2,9
1 Banting and Best Department of Medical Research, University of Toronto, Terrence Donnelly Center for Cellular and Biomolecular Research, Toronto, Ontario M5S 3E1, Canada; 2 Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada; 3 Molecular Biology Institute, Center for Genomics and Proteomics, Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA; 4 Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine and Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, Iowa, 52242, USA; 5 Division of Neuroscience and Center for Behavioral Neuroscience, Yerkes National Primate Research Center, and Department of Pathology, Emory University, Atlanta, Georgia 30329, USA; 6 Genes and Disease Program, Center for Genomic Regulation (CRG-UPF), 08003 Barcelona, Spain; 7 Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Alternative splicing is a powerful mechanism affording extensive proteomic and regulatory diversity from a limited repertoire of genes. However, the extent to which alternative splicing has contributed to the evolution of primate species-specific characteristics has not been assessed previously. Using comparative genomics and quantitative microarray profiling, we performed the first global analysis of alternative splicing differences between humans and chimpanzees. Surprisingly, 6%–8% of profiled orthologous exons display pronounced splicing level differences in the corresponding tissues from the two species. Little overlap is observed between the genes associated with alternative splicing differences and the genes that display steady-state transcript level differences, indicating that these layers of regulation have evolved rapidly to affect distinct subsets of genes in humans and chimpanzees. The alternative splicing differences we detected are predicted to affect diverse functions including gene expression, signal transduction, cell death, immune defense, and susceptibility to diseases. Differences in expression at the protein level of the major splice variant of Glutathione S-transferase omega-2 (GSTO2), which functions in the protection against oxidative stress and is associated with human aging-related diseases, suggests that this enzyme is less active in human cells compared with chimpanzee cells. The results of this study thus support an important role for alternative splicing in establishing differences between humans and chimpanzees.
[Keywords: Alternative splicing; gene regulation; microarray profiling; primate evolution]]
Received August 20, 2007; revised version accepted September 18, 2007.
