Genotype networks in metabolic reaction spaces

 

AREEJIT SAMAL

LABORATOIRE DE PHYSIQUE THÉORIQUE ET MODÈLES STATI

 

Background: A metabolic genotype comprises all chemical reactions an organism can catalyze via enzymes encoded in its genome. A genotype is viable in a given environment if it is capable of producing all biomass components the organism needs to survive and reproduce. Previous work has focused on the properties of individual genotypes while little is known about how genome-scale metabolic networks with a given function can vary in their reaction content. Results: We here characterize spaces of such genotypes. Specifically, we study metabolic genotypes whose phenotype is viability in minimal chemical environments that differ in their sole carbon sources. We show that regardless of the number of reactions in a metabolic genotype, viable genotypes form vast, connected, and unstructured sets of genotypes -- genotype networks -- that have the same phenotype and typically nearly span the whole of genotype space. The robustness of metabolic phenotypes to random reaction removal in such spaces has a narrow distribution with a high mean. Different carbon sources differ in the number of metabolic genotypes in their genotype network; this number decreases if a genotype is required to be viable on more than one carbon source, but much less than if the reactions were used independently across different chemical environments. Conclusions: Our work shows that phenotype-preserving genotype networks have generic organizational properties and that these properties are insensitive to the number of reactions in metabolic genotypes.