Global epistasis emerges from a generic model of a complex trait

Area of Science:

• Evolutionary biology
• Genetics
• Systems biology

Background:

• Epistasis, the interaction between mutations, can influence evolutionary adaptation.
• Microbial evolution experiments often display consistent fitness increases across replicate lines, despite known microscopic epistasis.
• Global epistasis patterns, such as diminishing returns and increasing costs, have been observed but their origin is unclear.

Purpose of the Study:

• To investigate the origin of global epistasis patterns in evolutionary systems.
• To determine if pervasive microscopic epistasis can generically lead to global epistasis.
• To explain the consistency of microbial evolution despite sequence-level stochasticity.

Main Methods:

• Development of a theoretical model to explore the consequences of pervasive microscopic epistasis.
• Quantitative analysis of the relationship between global epistasis magnitude and microscopic epistasis effects.
• Reanalysis of existing experimental data to validate model predictions.
• Introduction of a novel fitness landscape model.

Main Results:

• Diminishing-returns and increasing-costs epistasis emerge as a generic consequence of widespread microscopic epistasis.
• A specific quantitative relationship between global and microscopic epistasis was predicted and confirmed.
• The distribution of fitness effects exhibits a universal form under widespread epistasis.
• Phenotypic evolution can be repeatable despite sequence-level stochasticity.

Conclusions:

• Pervasive microscopic epistasis is sufficient to generate the global epistasis patterns observed in evolution.
• This provides a mechanistic explanation for the consistent evolutionary trajectories seen in replicate microbial populations.
• The findings offer insights into the predictability of evolution and the structure of fitness landscapes.