Epistasis and the Dynamics of Reversion in Molecular Evolution

Area of Science:

• Evolutionary biology
• Molecular evolution
• Biophysics

Background:

• Studies suggest that amino acid substitutions in protein evolution have decreasing reversion rates.
• The likelihood of reversion decreases as a substitution persists at a specific site.

Purpose of the Study:

• To rigorously investigate the phenomenon of decreasing reversion rates in protein evolution.
• To generalize the understanding of reversion rates in arbitrary fitness landscapes.

Main Methods:

• Mathematical modeling of protein evolution under weak mutation.
• Analysis of hazard functions for waiting times until reversion.
• Examination of sites involved in epistatic interactions.

Main Results:

• Reversion rates decrease with time for sites involved in at least one epistatic interaction.
• At stationarity, the hazard function for reversion waiting times is strictly decreasing for such sites.
• A common pattern shows rapid initial reversion probability followed by a plateau.

Conclusions:

• Epistasis significantly influences reversion rates, making them decrease over time.
• The longer a character is absent from a site, the less likely reversion becomes.
• Reversion tends to occur either very early or after a prolonged period.