Genotype networks in metabolic reaction spaces

TL;DR

This paper explores the structure of metabolic genotype networks, revealing they are large, connected, and robust, with properties consistent across different reaction counts and environmental conditions.

Contribution

It characterizes the organization and robustness of genotype networks in metabolic spaces, showing their extensive connectivity and insensitivity to reaction number variations.

Findings

Genotype networks are large, connected, and span most of the space.

Metabolic phenotypes exhibit high robustness to reaction loss.

Number of genotypes decreases with more environmental constraints.

Abstract

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, the genotypes of a given phenotype typically form vast, connected, and unstructured sets -- genotype networks -- that 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 as a genotype is required to be viable on increasing numbers of carbon sources, but much less than if metabolic 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.