Автор |
Werner, Maria |
Автор |
Aurell, Erik |
Дата выпуска |
2009-12-01 |
dc.description |
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. |
Формат |
application.pdf |
Издатель |
Institute of Physics Publishing |
Копирайт |
2009 IOP Publishing Ltd |
Название |
A computational study of λ-lac mutants |
Тип |
paper |
DOI |
10.1088/1478-3975/6/4/046007 |
Electronic ISSN |
1478-3975 |
Print ISSN |
1478-3967 |
Журнал |
Physical Biology |
Том |
6 |
Первая страница |
46007 |
Последняя страница |
46017 |
Аффилиация |
Werner, Maria; Department of Computational Biology, KTH—Royal Institute of Technology, Albanova University Center, SE-10691 Stockholm, Sweden |
Аффилиация |
Aurell, Erik; Department of Computational Biology, KTH—Royal Institute of Technology, Albanova University Center, SE-10691 Stockholm, Sweden |
Выпуск |
4 |