Multi-component gene network design as a survival strategy in diverse environments.
Multi-component gene network design as a survival strategy in diverse environments.
复制标题
DOI：
10.1186/s12918-018-0609-3
复制
发表时间：
2018-09-26
影响因子：
--
通讯作者：
Acar M
中科院分区：
文献类型：
--
作者：
Luo X;Song R;Acar M
基因-环境相互作用通常通过基因网络介导，其中基因表达产物与其他网络组分相互作用以决定网络活性水平，这反过来又决定了宿主细胞在特定环境中的适应性。尽管基因网络是研究基因-环境相互作用的合适背景，但我们对系统性遗传扰动如何影响基因网络背景下的适应度知之甚少。在这里，我们研究组合基因剂量改变对基因网络活性和细胞适应性的影响。使用半乳糖利用途径作为二倍体酵母中的模型网络，我们将四个调控基因（GAL 2，GAL 3，GAL 4，GAL 80）的拷贝数从两个减少到一个，并测量扰动网络的活性。我们整合这些结果与竞争力的健身测量在六个不同的合理设计的环境中含有不同的半乳糖浓度代表的半乳糖网络的自然诱导谱。在最低的半乳糖环境中，我们发现基因表达和健身之间的非线性关系，而高半乳糖环境导致两者之间的线性关系，在足够高的半乳糖浓度下达到饱和状态。我们进一步揭示了环境特定的相关性的不同的网络组件之间的关系的网络活动和生物体的健身，表明没有网络组件是冗余的。这些结果提供了实验支持的假设，在整个自然进化的环境中的动态变化是关键的结构自然基因网络在一个多组件的方式，强大的提供保护，防止人口灭绝在不同的环境。本文的在线版本（10.1186/s12918-018-0609-3）包含补充材料，可供授权用户使用。
Gene-environment interactions are often mediated though gene networks in which gene expression products interact with other network components to dictate network activity levels, which in turn determines the fitness of the host cell in specific environments. Even though a gene network is the right context for studying gene-environment interactions, we have little understanding on how systematic genetic perturbations affects fitness in the context of a gene network. Here we examine the effect of combinatorial gene dosage alterations on gene network activity and cellular fitness. Using the galactose utilization pathway as a model network in diploid yeast, we reduce the copy number of four regulatory genes (GAL2, GAL3, GAL4, GAL80) from two to one, and measure the activity of the perturbed networks. We integrate these results with competitive fitness measurements made in six different rationally-designed environments containing different galactose concentrations representing the natural induction spectrum of the galactose network. In the lowest galactose environment, we find a nonlinear relationship between gene expression and fitness while high galactose environments lead to a linear relationship between the two with a saturation regime reached at a sufficiently high galactose concentration. We further uncover environment-specific relevance of the different network components for dictating the relationship between the network activity and organismal fitness, indicating that none of the network components are redundant. These results provide experimental support to the hypothesis that dynamic changes in the environment throughout natural evolution is key to structuring natural gene networks in a multi-component fashion, which robustly provides protection against population extinction in different environments. The online version of this article (10.1186/s12918-018-0609-3) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
--
作者：
Song R;Peng W;Liu P;Acar M
通讯作者：
Acar M
影响因子：
3.3
作者：
da Silva, Jack;Coetzer, Mia;Mosier, Donald E.
通讯作者：
Mosier, Donald E.
影响因子：
8.8
作者：
Elison, Gregory L.;Song, Ruijie;Acar, Murat
通讯作者：
Acar, Murat
影响因子：
--
作者：
Song R;Liu P;Acar M
通讯作者：
Acar M
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y