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大型酵母种群中单细胞蛋白质丰度变化的遗传学

Frank W Albert¹, Sebastian Treusch², Arthur H Shockley³

¹1] Department of Human Genetics, University of California, Los Angeles, California 90095, USA [2] Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.

|January 10, 2014

概括

这项研究引入了一种新的方法,以找到影响酵母蛋白质水平的遗传联系. 该方法比以前的方法发现了更多影响蛋白质表达的基因位置,揭示了监管热点.

科学领域:

遗传学是一个遗传学.
分子生物学分子生物学
系统生物学系统生物学

背景情况:

遗传变异是特征和疾病的个人差异的基础,但遗传基础往往不清楚.
表达量的特征位点 (eQTL) 将DNA变异与基因表达联系起来,但使用mRNA的传统方法存在局限性.
之前对蛋白质定量特征位点 (pQTL) 的研究很少,并显示与eQTL的差异.

研究的目的:

开发一种强大的方法来识别影响蛋白质表达的基因位置.
研究Saccharomyces cerevisiae中蛋白质丰度变化的遗传基础.
将蛋白质水平的遗传影响与mRNA水平的影响进行比较.

主要方法:

用绿色光蛋白标签测量单细胞蛋白质的丰富性,用于大量的基因变异酵母细胞.
采用聚合测序来比较高与低蛋白质丰度的个体中的等位基因频率.
将该方法应用于160个基因,以检测影响蛋白质表达的基因位置.

主要成果:

与之前的研究相比,检测到每种影响蛋白质丰度的基因显著更多的遗传位置.
观察到影响蛋白质丰度的位点和影响mRNA丰度的位点之间更密切的对应.
鉴定了多种蛋白质共同影响的基因变异的"热点",其中一些影响了超过一半的检查蛋白质.

结论:

这种新方法有效地识别了大种群中调节蛋白质表达的遗传位置.
遗传"热点"在调节蛋白质丰度和基因网络方面发挥着重要作用.
研究结果提供了对影响酵母细胞生理学和调节网络的遗传变异的见解.

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