Perspective: Sign epistasis and genetic constraint on evolutionary trajectories

Area of Science:

• Evolutionary biology
• Genetics

Background:

• Epistasis, the phenomenon where a mutation's effect depends on the genetic background, is common but its evolutionary impact is not fully understood.
• Current research often focuses on epistasis's role in allele frequency changes, overlooking its influence on evolutionary trajectories.

Purpose of the Study:

• To explore the influence of genetic background on the selective accessibility of evolutionary trajectories.
• To investigate a specific form of epistasis, sign epistasis, and its evolutionary consequences.

Main Methods:

• Theoretical exploration of epistasis's influence on evolutionary pathways.
• Review of experimental literature, particularly from microbial systems, assessing mutation fitness effects across diverse genetic backgrounds.

Main Results:

• Identified and defined "sign epistasis," where a mutation's fitness effect (beneficial or deleterious) is determined by the genetic background.
• Found numerous examples of sign epistasis in recent microbial experimental studies.
• Demonstrated that sign epistasis can constrain the accessibility of high-fitness genotypes, independent of population polymorphism.

Conclusions:

• Sign epistasis represents a significant, yet often overlooked, factor in natural selection and evolution.
• The findings suggest substantial genetic constraints on evolutionary trajectories towards high fitness.
• Highlights the need for further research into the broader implications of sign epistasis across different organisms.