University of Zurich, Institute of Evolutionary Biology and Environmental Studies, Zurich, Switzerland.
PLoS Comput Biol. 2013;9(6):e1003071. doi: 10.1371/journal.pcbi.1003071. Epub 2013 Jun 6.
Gene regulatory circuits drive the development, physiology, and behavior of organisms from bacteria to humans. The phenotypes or functions of such circuits are embodied in the gene expression patterns they form. Regulatory circuits are typically multifunctional, forming distinct gene expression patterns in different embryonic stages, tissues, or physiological states. Any one circuit with a single function can be realized by many different regulatory genotypes. Multifunctionality presumably constrains this number, but we do not know to what extent. We here exhaustively characterize a genotype space harboring millions of model regulatory circuits and all their possible functions. As a circuit's number of functions increases, the number of genotypes with a given number of functions decreases exponentially but can remain very large for a modest number of functions. However, the sets of circuits that can form any one set of functions becomes increasingly fragmented. As a result, historical contingency becomes widespread in circuits with many functions. Whether a circuit can acquire an additional function in the course of its evolution becomes increasingly dependent on the function it already has. Circuits with many functions also become increasingly brittle and sensitive to mutation. These observations are generic properties of a broad class of circuits and independent of any one circuit genotype or phenotype.
基因调控回路驱动着从细菌到人类等生物体的发育、生理和行为。这些回路的表型或功能体现在它们形成的基因表达模式中。调控回路通常具有多功能性，在不同的胚胎阶段、组织或生理状态下形成不同的基因表达模式。任何一个具有单一功能的回路都可以由许多不同的调控基因型来实现。多功能性可能会限制这个数量，但我们不知道限制的程度。我们在这里详尽地描述了一个包含数百万个模型调控回路及其所有可能功能的基因型空间。随着回路功能数量的增加，给定功能数量的基因型数量呈指数级减少，但对于少量功能来说，数量仍然非常大。然而，能够形成任何一组功能的回路集合变得越来越碎片化。因此，在具有许多功能的回路中，历史偶然性变得越来越普遍。一个回路在其进化过程中是否能够获得额外的功能，越来越取决于它已经拥有的功能。具有许多功能的回路也变得越来越脆弱，对突变也越来越敏感。这些观察结果是广泛的一类回路的通用特性，与任何一个回路基因型或表型无关。
