  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.
