Correlations between Homeostasis and Genetic Robustness in Enzymatic Networks

The evolutionary fitness of an organism, a unitary concept, is defined as the likelihood that the lineage of that organism survives. A priori, this fitness requires that the organism can adapt to external/non-genetic perturbations (homeostasis) and that the transmitted genotype is robust to internal/genetic changes (genetic robustness) so as to preserve the success of the progenitor phenotype. Biologically and mathematically, a priori, these two concepts are unrelated: Homeostasis is a dynamic property and is a direct product of natural selection. Genetic robustness is a static property that is unnecessary for homeostasis. It is, however, essential for evolution to occur and seems to coexist with homeostasis in many biological processes. Despite its central role in the evolutionary process, the rationale for selection for genetic robustness is still controversial. It has been suggested that genetic robustness is a by-product of homeostasis but the origins of this putative relationship have never been investigated in a general theoretical context.Here, we find a strong statistical correlation between adaptive homeostasis and genetic robustness in N-node enzymatic networks, providing a foundation for the unitary character of evolutionary fitness. We investigate the scaling properties of these networks and extract topological motifs that are necessary and/or sufficient to achieve adaptive homeostasis and/or genetic robustness. Furthermore, we map out the robustness/homeostasis space of these topologies. This correlation and the identification of design principles renders the deciphering and reconstruction of complex biological networks more feasible as we narrow down the search space for possible design principles in biology.