[POS] Evolution and Genetics

[POS-47] Constraints on evolutionary pathways in evolutionary rescue: mutual feedback between population dynamics and the fitness Landscape

*Tokuya OGAWA OGAWA¹, Ryo Yamaguchi² (1. Graduate school of Life Science, Hokkaido University (Japan), 2. Department of Advanced Transdisciplinary Science, Hokkaido University (Japan))

Keywords:

Adaptive evolution,fitness landscape theory,population dynamics

Evolutionary rescue describes how genetic adaptation enables a population to recover from environmental stress that would otherwise cause extinction. Fitness landscape theory provides a framework for understanding adaptation to rapid environmental changes. On a fitness landscape, adaptive evolution of a population is metaphorically described as reaching a fitness peak while avoiding valleys. Negative gene-gene interactions known as sign epistasis, create fitness valleys and increase the complexity of the landscape, thereby serving as a major constraint on evolutionary pathways. However, populations must overcome the risk of extinction, and often require the accumulation of large-effect mutations to increase fitness rapidly. This suggests that constraints on evolutionary paths may underappreciate the role of population extinctions.We combined fitness landscape theory with the mathematical model. Specifically, we considered a landscape comprising 1024 genotypes (10 loci with 2 alleles each) based on Rough Mount Fuji (RMF) model, where fitness is determined by both additive effect—each allele contributing independently—and epistatic effects, wherein gene-gene interactions can synergistically or suppressively modify fitness. Our results indicate that, under specific parameter settings, the landscape imposes constraints that reduce accessible evolutionary paths by approximately 40%. Furthermore, the combined effects of sign epistasis and environmental stress further constrain evolutionary paths, making parallel evolution more likely to occur. In addition, successful evolutionary rescue depends on both the accumulation of multiple mutations in landscapes with strong additive effect, and the occurrence of large-effect mutations with strong epistatic contribution, highlighting the significant impact of landscape complexity on evolutionary rescue.In conclusion, we demonstrate that environmental stress constrains the emergence of small-effect mutations and subsequent evolutionary paths in the early stages of adaptation, and that the complexity of the adaptive landscape also contributes to determine the rate of evolutionary rescue.These results suggest that, in drug resistance evolution experiments, increasing the extinction risk by rapidly increasing drug concentrations may limit the evolutionary pathway in terms of population dynamics and limit the search for diverse resistance and global optimum drug resistance among the evolved strains.