The hidden potential of recombination inhibitors:
sidestepping the Darwinian inevitability of resistance?
Philip Gerrish
CMAF/ U Lisbon and U New Mexico
USA

Abstract

An obvious benefit of inhibiting recombination is to delay the emergence of multi-resistant strains of a pathogen. The magnitude of this delay, however, has been shown to be small. A much less obvious, but perhaps ultimately more effective, benefit has been implied in recent theoretical work and is beginning to be validated by experimental work: inhibiting recombination should destabilize a pathogen’s genome and trigger a self-reinforcing loss of replication fidelity – driven paradoxically by adaptation – that ultimately drives the pathogen to a precipitous decline in replication rate. Here, we present evidence from simulated populations suggesting that a hypothetical recombination inhibitor could drive this process of lethal genomic destabilization without the evolution of resistance to the inhibitor, despite the appearance of one resistant mutant arising in the population on average every generation.

Jornada Matemática SPM/CIM "Mathematical Biology"