The pathway kinetics model depicts the mechanisms of the "decision circuit" that commits a bacterial virus [lambda] to one of two alternate pathways in its life cycle. The lytic path sets the stage for immediate replication of the virus and destruction of its Escherichia coli host cell, while the lysogenic path selects for the incorporation of viral DNA into the host genome, allowing the virus to remain in a dormant state. In the diagram, bold horizontal lines indicate stretches of double-stranded DNA, arrows over genes show the transcription direction, and dashed boxes enclose operator sites that comprise a promoter control complex. The core of the decision circuit is the four-promoter, five-gene regulatory network; initiation of pathway actions involve other coupled genes not shown. Many pathogenic organisms use a similar mechanism of concentration-independent probabilistic pathway selection to switch surface features and evade host responses. In the model above, pathway selection at different virus concentrations, predicted using a kinetic model of the genetic regulatory circuit, is consistent with experimental observations. Developing this model required nearly 40 empirical rate constants and the use of a supercomputer.
Credit or Source: Adapted from A. Arkin, J. Ross, and H. H. McAdams, Genetics 149, 1633-48 (1998). Credit or Source: Office of Biological and Environmental Research of the U.S. Department of Energy Office of Science. science.energy.gov/ber/
Genomes to Life Program Roadmap, April 2001, DOE/SC-0036, U.S. Department of Energy Office of Science. (website)