A computational study of λ-lac mutants
Werner, Maria; Aurell, Erik; Werner, Maria; Department of Computational Biology, KTH—Royal Institute of Technology, Albanova University Center, SE-10691 Stockholm, Sweden; Aurell, Erik; Department of Computational Biology, KTH—Royal Institute of Technology, Albanova University Center, SE-10691 Stockholm, Sweden
Журнал:
Physical Biology
Дата:
2009-12-01
Аннотация:
We present a comprehensive, computational study of the properties of bacteriophage λ mutants designed by Atsumi and Little (2006 Proc. Natl. Acad. Sci. 103 4558-63). These phages underwent a genetic reconstruction where Cro was replaced by a dimeric form of the Lac repressor. To clarify the theoretical characteristics of these mutants, we built a detailed thermodynamic model. The mutants all have a different genetic wiring than the wild-type λ. One group lacks regulation of P<sub>RM</sub> by the lytic protein. These mutants only exhibit the lysogenic equilibrium, with no transiently active P<sub>R</sub>. The other group lacks the negative feedback from CI. In this group, we identify a handful of bi-stable mutants, although the majority only exhibit the lysogenic equilibrium. The experimental identification of functional phages differs from our predictions. From a theoretical perspective, there is no reason why only 4 out of 900 mutants should be functional. The differences between theory and experiment can be explained in two ways. Either, the view of the λ phage as a bi-stable system needs to be revised, or the mutants have in fact not undergone a modular replacement, as intended by Atsumi and Little, but constitute instead a wider systemic change.
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