Mol Cell.: 基因突变的“连锁”反应

 

    约翰霍普金斯大学科学家发现在酵母中删除任何一个基因都会对基因组产生压力,造成其他基因的突变。研究人员称该发现对人类遗传学有启示作用,因为DNA在物种之间是保守的,该研究对癌症和其他领域的遗传分析有重要意义。相关报道发表在近期的Molecular Cell杂志上。
 
    该文章的通讯作者J. Marie Hardwick博士称,删除任何一个基因往往会导致另一个有时候是两个基因的连锁反应。对比原始突变基因和二次突变基因将会让我们了解到大量的之前未知的基因联系。
 
    科学家随机选取了250个单基因突变株,每一株又产生六个亚株。然后对每一个亚株进行"压力测试"。最终科学家发现77%的突变株另外又获得了一个或两个突变。
 
    Hardwick博士称,以后科学家要重新审视他们的遗传操作,因为诱导的基因突变产生的现象有可能是二次突变造成的。
 

    Hardwick博士称,该研究在癌症领域中重要的应用前景。我们认为癌症发展过程是最开始单一抑癌基因突变导致一些列的突变的过程。我们希望在酵母中找到肿瘤发展过程中"最开始的"突变基因。

   

Genome-wide Consequences of Deleting Any Single Gene

 

 
Teng X, Dayhoff-Brannigan M, Cheng WC, Gilbert CE, Sing CN, Diny NL, Wheelan SJ, Dunham MJ, Boeke JD, Pineda FJ, Hardwick JM.

 

Loss or duplication of chromosome segments can lead to further genomic changes associated with cancer. However, it is not known whether only a select subset of genes is responsible for driving further changes. To determine whether perturbation of any given gene in a genome suffices to drive subsequent genetic changes, we analyzed the yeast knockout collection for secondary mutations of functional consequence. Unlike wild-type, most gene knockout strains were found to have one additional mutant gene affecting nutrient responses and/or heat-stress-induced cell death. Moreover, independent knockouts of the same gene often evolved mutations in the same secondary gene. Genome sequencing identified acquired mutations in several human tumor suppressor homologs. Thus, mutation of any single gene may cause a genomic imbalance, with consequences sufficient to drive adaptive genetic changes. This complicates genetic analyses but is a logical consequence of losing a functional unit originally acquired under pressure during evolution.