Early effects of gene duplication on the robustness and phenotypic variability of gene regulatory networks.

Background: Research on gene duplication is abundant and comes from a wide range of approaches, from high-throughput analyses and experimental evolution to bioinformatics and theoretical models. Notwithstanding, a consensus is still lacking regarding evolutionary mechanisms involved in evolution through gene duplication as well as the conditions that affect them. We argue that a better understanding of evolution through gene duplication requires considering explicitly that genes do not act in isolation. It demands studying how the perturbation that gene duplication implies percolates through the web of gene interactions. Due to evolution's contingent nature, the paths that lead to the final fate of duplicates must depend strongly on the early stages of gene duplication, before gene copies have accumulated distinctive changes.

Methods: Here we use a widely-known model of gene regulatory networks to study how gene duplication affects network behavior in early stages. Such networks comprise sets of genes that cross-regulate. They organize gene activity creating the gene expression patterns that give cells their phenotypic properties. We focus on how duplication affects two evolutionarily relevant properties of gene regulatory networks: mitigation of the effect of new mutations and access to new phenotypic variants through mutation.

Results: Among other observations, we find that those networks that are better at maintaining the original phenotype after duplication are usually also better at buffering the effect of single interaction mutations and that duplication tends to enhance further this ability. Moreover, the effect of mutations after duplication depends on both the kind of mutation and genes involved in it. We also found that those phenotypes that had easier access through mutation before duplication had higher chances of remaining accessible through new mutations after duplication.

Conclusion: Our results support that gene duplication often mitigates the impact of new mutations and that this effect is not merely due to changes in the number of genes. The work that we put forward helps to identify conditions under which gene duplication may enhance evolvability and robustness to mutations.