2024/05/24 by Nicholas L. V. O’Brien, Barbara R. Holland, Jan Engelstädter +1 · 1 voice
Biochemistry, Genetics and Molecular Biology · Social Sciences · #Evolution and Genetic Dynamics #Gene Regulatory Network Analysis #Evolutionary Game Theory and Cooperation
paper · pdf · doi:10.1371/journal.pgen.1011289
openalex publication_date 2024/05/24 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/27
The tempo and mode of adaptation depends on the availability of beneficial alleles. Genetic interactions arising from gene networks can restrict this availability. However, the extent to which networks affect adaptation remains largely unknown. Current models of evolution consider additive genotype-phenotype relationships while often ignoring the contribution of gene interactions to phenotypic variance. In this study, we model a quantitative trait as the product of a simple gene regulatory network, the negative autoregulation motif. Using forward-time genetic simulations, we measure adaptive walks towards a phenotypic optimum in both additive and network models. A key expectation from adaptive walk theory is that the distribution of fitness effects of new beneficial mutations is exponential. We found that both models instead harbored distributions with fewer large-effect beneficial alleles than expected. The network model also had a complex and bimodal distribution of fitness effects among all mutations, with a considerable density at deleterious selection coefficients. This behavior is reminiscent of the cost of complexity, where correlations among traits constrain adaptation. Our results suggest that the interactions emerging from genetic networks can generate complex and multimodal distributions of fitness effects.