EMBL-CRG Systems Biology Research Unit, Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain.
Mol Syst Biol. 2013;9:645. doi: 10.1038/msb.2013.2.
Reduced activity of two genes in combination often has a more detrimental effect than expected. Such epistatic interactions not only occur when genes are mutated but also due to variation in gene expression, including among isogenic individuals in a controlled environment. We hypothesized that these 'epigenetic' epistatic interactions could place important constraints on the evolution of gene expression. Consistent with this, we show here that yeast genes with many epistatic interaction partners typically show low expression variation among isogenic individuals and low variation across different conditions. In addition, their expression tends to remain stable in response to the accumulation of mutations and only diverges slowly between strains and species. Yeast promoter architectures, the retention of gene duplicates, and the divergence of expression between humans and chimps are also consistent with selective pressure to reduce the likelihood of harmful epigenetic epistatic interactions. Based on these and previous analyses, we propose that the tight regulation of epistatic interaction network hubs makes an important contribution to the maintenance of a robust, 'canalized' phenotype. Moreover, that epigenetic epistatic interactions may contribute substantially to fitness defects when single genes are deleted.
两种基因活性降低的组合往往比预期的更具危害性。这种上位性相互作用不仅发生在基因突变时，也发生在基因表达的变化中，包括在受控环境中同基因个体之间。我们假设这些“表观遗传”上位性相互作用可能对基因表达的进化产生重要限制。与这一假设一致，我们在这里表明，与同基因个体之间的表达变化较小且在不同条件下的变化较小的酵母基因具有许多上位性相互作用伙伴。此外，它们的表达倾向于在响应突变积累时保持稳定，并且在菌株和物种之间仅缓慢发散。酵母启动子结构、基因重复的保留以及人类和黑猩猩之间的表达差异也与降低有害表观遗传上位性相互作用可能性的选择压力一致。基于这些和以前的分析，我们提出，上位性相互作用网络枢纽的紧密调控对维持稳健的“管化”表型做出了重要贡献。此外，当单个基因缺失时，表观遗传上位性相互作用可能会导致大量的适应性缺陷。
