Nature：基因组复制或为解析癌症进化提供线索

  有机体细胞中的基因组拷贝数越多，细胞或越易于从生长和适应中获益。近日，一篇刊登于国际杂志Nature上的研究论文中，来自克瑞顿大学（Creighton University）的研究人员通过对酵母菌的研究发现，多倍体或许可以极大地帮助细胞去适应周围的环境，多倍体即有机体细胞中的基因组拷贝数超过2倍，由于癌细胞通常都为多倍体或非整倍体，因此本文的研究结果或为进行癌症研究提供新的线索。

  研究者Selmecki说道，拥有额外的基因组拷贝可以促进酵母在环境中进行更快速地适应过程，本研究看起来似乎是一项非常简单的研究，但我们可以对比不同二倍体细胞的适应率，就好像是组成我们机体的遗传相同的二倍体细胞一样，随后研究者对大约75名个体进行了全基因组的测序来观察这些细胞在实验中是如何去适应环境的。

  研究者表示，他们对大量酵母细胞为何会开始形成多倍体非常感兴趣；在癌细胞中，许多肿瘤细胞会经历基因组加倍变成四倍体肿瘤细胞，一旦这样许多基因突变就会被放大，并且快速表现出来，因此有效控制癌细胞加倍基因组或许可以帮助进行癌症诊断和相应疗法的开发。

  利用基因组、细胞生物学、进化论及数学模型进行相关研究后，研究者Selmecki的研究引起了美国癌症协会的注意，其或许可以为这项研究进行部分资金的资助，研究者的长期研究目标就是继续进行基因组进化的研究来帮助发现治疗癌症及其它疾病的新型疗法。

  最后研究者说道，目前还有许多问题需要去解决，为何哺乳动物更易于进化出二倍体细胞，而其它物种比如植物则更易于进化出多倍体细胞？在其它有机体中基因组加倍的频率是多久？引发的结果又是什么？后期研究人员将带着这一系列问题进行更为深入的研究。（转化医学网360zhyx.com）

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转化医学网推荐的原文阅读：

Polyploidy can drive rapid adaptation in yeast
Nature doi:10.1038/nature14187
Anna M. Selmecki, Yosef E. Maruvka, Phillip A. Richmond, Marie Guillet, Noam Shoresh, Amber L. Sorenson, Subhajyoti De, Roy Kishony, Franziska Michor, Robin Dowell & David Pellman
Polyploidy is observed across the tree of life, yet its influence on evolution remains incompletely understood1, 2, 3, 4. Polyploidy, usually whole-genome duplication, is proposed to alter the rate of evolutionary adaptation. This could occur through complex effects on the frequency or fitness of beneficial mutations2, 5, 6, 7. For example, in diverse cell types and organisms, immediately after a whole-genome duplication, newly formed polyploids missegregate chromosomes and undergo genetic instability8, 9, 10, 11, 12, 13. The instability following whole-genome duplications is thought to provide adaptive mutations in microorganisms13, 14 and can promote tumorigenesis in mammalian cells11, 15. Polyploidy may also affect adaptation independently of beneficial mutations through ploidy-specific changes in cell physiology16. Here we perform in vitro evolution experiments to test directly whether polyploidy can accelerate evolutionary adaptation. Compared with haploids and diploids, tetraploids undergo significantly faster adaptation. Mathematical modelling suggests that rapid adaptation of tetraploids is driven by higher rates of beneficial mutations with stronger fitness effects, which is supported by whole-genome sequencing and phenotypic analyses of evolved clones. Chromosome aneuploidy, concerted chromosome loss, and point mutations all provide large fitness gains. We identify several mutations whose beneficial effects are manifest specifically in the tetraploid strains. Together, these results provide direct quantitative evidence that in some environments polyploidy can accelerate evolutionary adaptation.