A computational study of lambda-lac mutants
2009 (English)In: PHYS BIOL, ISSN 1478-3967, Vol. 6, no 4Article in journal (Refereed) Published
We present a comprehensive, computational study of the properties of bacteriophage lambda 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. lambda One group lacks regulation of P-RM by the lytic protein. These mutants only exhibit the lysogenic equilibrium, with no transiently active P-R. 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 lambda 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.
Place, publisher, year, edition, pages
2009. Vol. 6, no 4
BACTERIOPHAGE-LAMBDA, ESCHERICHIA-COLI, CI REPRESSOR, TRANSCRIPTIONAL REGULATION, PROPHAGE INDUCTION, GENE-REGULATION, PHAGE-LAMBDA, OPERATOR DNA, CRO, BINDING
IdentifiersURN: urn:nbn:se:kth:diva-12092DOI: 10.1088/1478-3975/6/4/046007ISI: 000272190400007ScopusID: 2-s2.0-70350722026OAI: oai:DiVA.org:kth-12092DiVA: diva2:301252