Variability in gene expression underlies incomplete penetrance.
Variability in gene expression underlies incomplete penetrance.
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个体生物之间的表型差异通常可以归因于潜在的遗传和环境变异。然而，即使是基因相同的生物在同质环境中也会有所不同，这表明基因表达等发育过程的随机性也可能产生多样性。为了研究基因表达变异性在多细胞生物中的影响，我们研究了秀丽隐杆线虫（Caenorhabditis elegans）的肠道规格，其中野生型细胞命运是不变的，由一个小的转录网络控制。该网络中元素的突变可能产生不确定的影响：一些突变胚胎不能发育肠细胞，而另一些则产生肠前体。通过计算个体胚胎中该网络中基因的转录本，我们发现，在突变体中，一个冗余基因的表达变得高度可变，并且这种变异是阈值，从而产生肠道分化的主调控基因的ON/OFF表达模式。我们的研究结果表明，发育网络中的突变可以暴露基因表达中的随机变异，从而导致明显的表型变异。
The phenotypic differences between individual organisms can often be ascribed to underlying genetic and environmental variation. However, even genetically identical organisms in homogenous environments vary, suggesting that randomness in developmental processes such as gene expression may also generate diversity. In order to examine the consequences of gene expression variability in multicellular organisms, we studied intestinal specification in the roundworm Caenorhabditis elegans in which wild-type cell fate is invariant and controlled by a small transcriptional network. Mutations in elements of this network can have indeterminate effects: some mutant embryos fail to develop intestinal cells, while others produce intestinal precursors. By counting transcripts of the genes in this network in individual embryos, we show that the expression of an otherwise redundant gene becomes highly variable in the mutants and that this variation is thresholded to produce an ON/OFF expression pattern of the master regulatory gene of intestinal differentiation. Our results demonstrate that mutations in developmental networks can expose otherwise buffered stochastic variability in gene expression, leading to pronounced phenotypic variation.
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