Noncommutative Biology: Sequential Regulation of Complex Networks

摘要

Author Summary DNA is the blueprint of life. Yet the order in which a cell follows these instructions makes it capable of generating thousands of different fates. How this information is extracted from underlying gene regulatory networks is unclear, especially given that biological networks are highly interconnected, and that the number of signaling pathways is relatively small (approximately 5 10). The conventional approach for increasing the information capacity of a limited set of regulators is to use them in combination. Surprisingly, combinatorial logic does not increase the diversity of target configurations or cell fates, but instead causes information bottlenecks. A different approach, called sequential logic, uses noncommutative sequences of a small set of regulators to drive networks to a large number of novel configurations. If certain targets are first protected, then even promiscuous regulators can activate specific subsets of lineage-specific targets. In this paper we show how sequential logic outperforms combinatorial logic, and argue that noncommutative sequences underlie a number of cases of biological regulation, e.g. how a small number of signaling pathways generates a large diversity of cell types in development. In addition to explaining biological networks, sequential logic may be a general experimental design strategy in synthetic and single-cell biology.