Origin and consequences of the relationship between protein mean and variance.
Origin and consequences of the relationship between protein mean and variance.
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DOI：
10.1371/journal.pone.0102202
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Mitra RD
中科院分区：
文献类型：
--
作者：
Vallania FL;Sherman M;Goodwin Z;Mogno I;Cohen BA;Mitra RD
蛋白质水平的细胞间差异（噪音）是一种普遍存在的现象，可以通过在细胞克隆群体中产生表型差异来增加适应性。一个重要的挑战是确定控制噪音的特定分子事件。蛋白质的细胞间差异通过幂律关系（σ 2 μ 1.69）对其平均表达水平的强烈依赖性使这项任务变得复杂。在这里，我们剖析这种关系的性质，使用一个随机模型参数化的实验测量值。该框架自然地概括了幂律关系（σ 2 = μ 1.6），并准确地预测了酵母蛋白质组中的蛋白质方差（r2 = 0.935）。 使用这个模型，我们确定了两种不同的机制，蛋白质的方差可以增加。影响启动子激活的变量，如核小体定位，通过改变幂律关系的指数来增加蛋白质方差。相反，影响启动子激活下游过程的变量，如mRNA和蛋白质合成，以幂律的平均依赖方式增加蛋白质方差。我们使用酵母中的诱导型基因表达系统实验验证了我们的发现。我们得出结论，噪声和蛋白质平均值之间的幂律关系是由于启动子激活的动力学。我们的研究结果为理解分子过程如何在基因组中形成随机变异提供了一个框架。
Cell-to-cell variance in protein levels (noise) is a ubiquitous phenomenon that can increase fitness by generating phenotypic differences within clonal populations of cells. An important challenge is to identify the specific molecular events that control noise. This task is complicated by the strong dependence of a protein's cell-to-cell variance on its mean expression level through a power-law like relationship (σ2∝μ1.69). Here, we dissect the nature of this relationship using a stochastic model parameterized with experimentally measured values. This framework naturally recapitulates the power-law like relationship (σ2∝μ1.6) and accurately predicts protein variance across the yeast proteome (r2 = 0.935). Using this model we identified two distinct mechanisms by which protein variance can be increased. Variables that affect promoter activation, such as nucleosome positioning, increase protein variance by changing the exponent of the power-law relationship. In contrast, variables that affect processes downstream of promoter activation, such as mRNA and protein synthesis, increase protein variance in a mean-dependent manner following the power-law. We verified our findings experimentally using an inducible gene expression system in yeast. We conclude that the power-law-like relationship between noise and protein mean is due to the kinetics of promoter activation. Our results provide a framework for understanding how molecular processes shape stochastic variation across the genome.
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DOI：
10.1126/science.1202142
发表时间：
2011-04-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Larson DR;Zenklusen D;Wu B;Chao JA;Singer RH
通讯作者：
Singer RH
影响因子：
16
作者：
Hornung, Gil;Oren, Moshe;Barkai, Naama
通讯作者：
Barkai, Naama
影响因子：
64.5
作者：
Basehoar, AD;Zanton, SJ;Pugh, BF
通讯作者：
Pugh, BF
影响因子：
16
作者：
Blake, William J.;Balazsi, Gbor;Collins, James J.
通讯作者：
Collins, James J.
影响因子：
64.8
作者：
Chang, Hannah H.;Hemberg, Martin;Huang, Sui
通讯作者：
Huang, Sui