Modeling of quantitative mutations.

We characterize mutations by a decrease in enzyme efficiency with respect to a wild-type “reference”, or “maximum” value. A: To find the wild-type lower and upper bounds of each reaction r, and , we expose the yeast metabolism to a series of environmental and genetic conditions and compute the minimum and maximum fluxes observed in the solutions taking into account their reversibility. Specifically, we compute pairs of optimal solutions in 104 random media from a totally unbounded and a randomly bounded yeast metabolisms (random bounds change in every medium; Methods). The bound for a given mutant and reaction is the product of the corresponding wild-type bound and a fractional value resulting from the quantitative interpretation of the associated gene reaction rule. B: Here we show a detailed example involving the malate synthase reaction MALSp which is mediated by two isozymes dal7 and mls1. The mutant upper bound, where denotes mutant, is the product of the wild-type upper bound and the result of the gene reaction rule δMALSp. C: The gene reaction rule in the case of MALSp reads “dal7 or mls1”, so we compute the sum of the relative gene dosages in the mutant of enzymes dal7 and mls1, and respectively. (TIF)