University of Zurich.
Artif Life. 2014 Winter;20(1):111-26. doi: 10.1162/ARTL_a_00099. Epub 2013 Feb 1.
In gene regulatory circuits, the expression of individual genes is commonly modulated by a set of regulating gene products, which bind to a gene's cis-regulatory region. This region encodes an input-output function, referred to as signal-integration logic, that maps a specific combination of regulatory signals (inputs) to a particular expression state (output) of a gene. The space of all possible signal-integration functions is vast and the mapping from input to output is many-to-one: For the same set of inputs, many functions (genotypes) yield the same expression output (phenotype). Here, we exhaustively enumerate the set of signal-integration functions that yield identical gene expression patterns within a computational model of gene regulatory circuits. Our goal is to characterize the relationship between robustness and evolvability in the signal-integration space of regulatory circuits, and to understand how these properties vary between the genotypic and phenotypic scales. Among other results, we find that the distributions of genotypic robustness are skewed, so that the majority of signal-integration functions are robust to perturbation. We show that the connected set of genotypes that make up a given phenotype are constrained to specific regions of the space of all possible signal-integration functions, but that as the distance between genotypes increases, so does their capacity for unique innovations. In addition, we find that robust phenotypes are (i) evolvable, (ii) easily identified by random mutation, and (iii) mutationally biased toward other robust phenotypes. We explore the implications of these latter observations for mutation-based evolution by conducting random walks between randomly chosen source and target phenotypes. We demonstrate that the time required to identify the target phenotype is independent of the properties of the source phenotype.
在基因调控回路中,单个基因的表达通常受到一组调节基因产物的调节,这些产物与基因的顺式调控区域结合。这个区域编码了一个输入-输出函数,称为信号整合逻辑,它将特定的调节信号组合(输入)映射到基因的特定表达状态(输出)。所有可能的信号整合函数的空间是巨大的,输入到输出的映射是多对一的:对于相同的输入集,许多函数(基因型)产生相同的表达输出(表型)。在这里,我们在基因调控回路的计算模型中穷举了产生相同基因表达模式的信号整合函数集。我们的目标是描述调控回路信号整合空间中的稳健性和可进化性之间的关系,并了解这些特性在基因型和表型尺度之间的变化。除其他结果外,我们发现基因型稳健性的分布是偏态的,因此大多数信号整合函数对扰动具有稳健性。我们表明,构成给定表型的基因型的连通集被约束在所有可能的信号整合函数空间的特定区域内,但随着基因型之间的距离增加,它们进行独特创新的能力也会增加。此外,我们发现稳健的表型是(i)可进化的,(ii)容易通过随机突变识别,以及(iii)突变偏向于其他稳健的表型。我们通过在随机选择的源和目标表型之间进行随机游走来探索这些观察结果对基于突变的进化的影响。我们证明,识别目标表型所需的时间与源表型的性质无关。