Evolution of resistance under alternative models of selective interference

Area of Science:

• Evolutionary biology
• Population genetics
• Molecular evolution

Background:

• Multiple pesticides/drugs exert simultaneous selection pressure for resistance alleles at different genetic loci.
• Models of resistance evolution often overlook how interference can reduce the probability of resistance allele spread.

Purpose of the Study:

• To examine the effects of selective interference on the fixation probability and time of a new, strongly beneficial mutation.
• To compare additive and multiplicative fitness models under strong selection relevant to resistance evolution.

Main Methods:

• Utilized computer simulations to model the fixation probability and time of beneficial mutations.
• Investigated the impact of a pre-existing beneficial allele at varying frequencies on a new beneficial mutation.
• Compared outcomes under additive and multiplicative fitness constructions.

Main Results:

• Under multiplicativity, interference caused minor reductions (up to ~10%) in fixation probability and negligible increases (~2%) in fixation time.
• Under additivity, interference led to substantial reductions (up to ~50%) in fixation probability and significant increases (up to ~100%) in fixation time.
• Interference significantly impacts resistance evolution primarily under additive fitness models.

Conclusions:

• Selective interference is a crucial factor in resistance evolution, particularly under additive fitness scenarios.
• Experimental evolution studies support additive models, suggesting resistance evolves via sequential selection of large-effect alleles rather than gradual selection of small-effect alleles.