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Expected Effect of Deleterious Mutations on Within-Host Adaptation of Pathogens.

Authors
Type
Published Article
Journal
Journal of Virology
1098-5514
Publisher
American Society for Microbiology
Publication Date
Volume
89
Issue
18
Pages
9242–9251
Identifiers
DOI: 10.1128/JVI.00832-15
PMID: 26109724
Source
Medline
License
Unknown

Abstract

Adaptation is critical for pathogens after zoonotic transmission into a new host species or to achieve antigenic immune escape and drug resistance. Using a deterministic approach, the effects of deleterious intermediate mutations on pathogen adaptation were calculated while avoiding commonly made simplifications that do not apply to large pathogen populations replicating with high mutation rates. Perhaps unexpectedly, pathogen adaptation does not halt when the intermediate mutations are fully deleterious. The negative effects of deleterious mutations are substantially outweighed by the fitness gains of adaptation. To gain an understanding of the effect of deleterious mutations on pathogen adaptation, a simple approach that counts the number of routes available to the pathogen with and without deleterious intermediate mutations is introduced. This methodology enables a straightforward calculation of the proportion of the pathogen population that will cross a fitness valley or traverse a fitness ridge, without reverting to more complicated mathematical models.

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