A computational systems biology study of the lambda-lac mutants

TL;DR

This study uses computational systems biology to analyze 900 lambda-lac mutants, revealing discrepancies with experimental data and suggesting complex mechanisms behind lysogeny and inducibility.

Contribution

It provides a comprehensive computational analysis of lambda-lac mutants, highlighting potential limitations of current mechanistic models and proposing the need for considering additional molecular factors.

Findings

Most mutants lack stable lytic states or are hard to induce.

Computational results contradict experimental findings for four mutants.

Suggests lysogeny and inducibility involve holistic effects and other mechanisms.

Abstract

We present a comprehensive computational study of some 900 possible "lambda-lac" mutants of the lysogeny maintenance switch in phage lambda, of which up to date 19 have been studied experimentally (Atsumi & Little, PNAS 103: 4558-4563, (2006)). We clarify that these mutants realise regulatory schemes quite different from wild-type lambda, and can therefore be expected to behave differently, within the conventional mechanistic setting in which this problem has often been framed. We verify that indeed, within this framework, across this wide selection of mutants the lambda-lac mutants for the most part either have no stable lytic states, or should only be inducible with difficulty. In particular, the computational results contradicts the experimental finding that four lambda-lac mutants both show stable lysogeny and are inducible. This work hence suggests either that the four out of 900 mutants are special, or that lambda lysogeny and inducibility are holistic effects involving other molecular players or other mechanisms, or both. The approach illustrates the power and versatility of computational systems biology to systematically and quickly test a wide variety of examples and alternative hypotheses for future closer experimental studies.