Error-threshold exists in fitness landscapes with lethal mutants

Area of Science:

• Evolutionary biology
• Theoretical biology
• Population genetics

Background:

• Quasi-species theory posits an error-threshold beyond which evolutionary optimization breaks down.
• Previous work suggested this threshold disappears when lethal mutants are considered.
• This study re-evaluates the error-threshold in high-dimensional genotype spaces, relaxing adjacency mutation assumptions.

Discussion:

• The study extends quasi-species equations to include mutant lethality, assuming uniform distribution of lethal genotypes.
• It analyzes mutation-selection dynamics in a multiplicative fitness landscape, considering both forward and back mutations.
• The impact of lethality on population distribution and ancestor distribution is investigated as a function of error rate.

Key Insights:

• High mutant lethality re-establishes an error-threshold in multiplicative fitness landscapes, contradicting prior conclusions.
• Population delocalization from the fittest genotype occurs at mutation rates significantly lower than random replication.
• These findings hold true irrespective of mutant lethality and extend to finite populations.

Outlook:

• This research refines our understanding of evolutionary constraints imposed by mutation rates and lethality.
• It highlights the importance of genotype space dimensionality and mutation patterns in evolutionary dynamics.
• The findings have implications for understanding viral evolution and the development of antiviral strategies.