2013年11月14 日訊 /生物谷BIOON/--約翰霍普金斯大學科學家發(fā)現(xiàn)在酵母中刪除任何一個基因都會對基因組產生壓力,,造成其他基因的突變,。研究人員稱該發(fā)現(xiàn)對人類遺傳學有啟示作用,因為DNA序列在物種之間具有保守性,,該研究對癌癥和其他領域的遺傳分析有重要意義,。相關報道發(fā)表在近期的Molecular Cell雜志上。
該文章的通訊作者J. Marie Hardwick博士稱,,剔除任何一個基因往往會導致另一個(有時候是兩個)基因的連鎖反應,。對比原始突變基因和二次突變基因將會讓我們了解到大量的之前未知的基因聯(lián)系。
科學家隨機選取了250個單基因突變株,,每一株又產生六個亞株,。然后對每一個亞株進行"壓力測試"。最終科學家發(fā)現(xiàn)77%的突變株另外又獲得了一個或兩個突變,。
Hardwick博士稱,,以后科學家要重新審視他們的遺傳操作,因為誘導的基因突變產生的現(xiàn)象有可能是二次突變造成的。
Hardwick博士稱,,該研究在癌癥領域中重要的應用前景,。我們認為癌癥發(fā)展過程是最開始單一抑癌基因突變導致一些列的突變的過程。我們希望在酵母中找到腫瘤發(fā)展過程中"最開始的"突變基因,。(生物谷Bioon.com)
doi:10.1016/j.molcel.2013.09.026
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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.