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基因组的变异. 从RNA到蛋白质的调节变化的影响

Alexis Battle¹, Zia Khan², Sidney H Wang²

¹Department of Genetics, Stanford University, Stanford, CA 94305, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.

Science (New York, N.Y.)

|February 7, 2015

概括

遗传变异影响蛋白质水平,但表达量性特征位点 (eQTLs) 对蛋白质丰度的影响较小. 一些遗传变异影响蛋白质水平独立于RNA或核糖体水平,表明后翻译调节.

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:

遗传变异的表型后果通常归因于蛋白质表达的变化.
遗传变异对蛋白质水平的确切影响,包括表达定量特征位点 (eQTLs),尚不清楚.
了解这些关系对于将基因型与表型联系起来至关重要.

研究的目的:

绘制与转录表达 (eQTLs),核糖体占用率 (rQTLs) 和蛋白质丰富度 (pQTLs) 相关的遗传变异.
为了研究基因变异和分子水平之间的关系,跨越中央教条.
确定遗传变异影响蛋白质水平的机制.

主要方法:

进行了全基因组关联研究,以确定基因表达,核糖体占用率和蛋白质丰度的定量特征位置 (QTL).
使用统计方法将遗传变异与不同的分子QTL联系起来.
对不同分子水平的QTL效应大小进行了比较.

主要成果:

大多数QTL与转录表达水平相关,影响核糖体和蛋白质水平.
与转录水平相比,eQTLs在蛋白质水平上显著减少了效果大小,这表明缓冲或减弱.
一个cis-QTLs子集直接影响了蛋白质丰度,对mRNA或核糖体水平的影响很小,这表明了翻译后调节.

结论:

遗传变异影响从RNA到蛋白质的分子水平,但效应并不总是线性传播.
由于对蛋白质丰度的影响减少,eQTL对下游表型的影响可能会减弱.
后翻译调节机制代表了对蛋白质水平的显著基因控制层,独立于转录和翻译效率.

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