title: Costs and benefits of mutational robustness in RNA viruses.
abstract: The accumulation of mutations in RNA viruses is thought to facilitate rapid adaptation to changes in the environment. However, most mutations have deleterious effects on fitness, especially for viruses. Thus, tolerance to mutations should determine the nature and extent of genetic diversity that can be maintained in the population. Here, we combine population genetics theory, computer simulation, and experimental evolution to examine the advantages and disadvantages of tolerance to mutations, also known as mutational robustness. We find that mutational robustness increases neutral diversity and, as expected, can facilitate adaptation to a new environment. Surprisingly, under certain conditions, robustness may also be an impediment for viral adaptation, if a highly diverse population contains a large proportion of previously neutral mutations that are deleterious in the new environment. These findings may inform therapeutic strategies that cause extinction of otherwise robust viral populations.
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Adi
authors.initials: A
authors.lastname: Stern
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA; IBM Research-Almaden, Industrial and Applied Genomics, 650 Harry Road, San Jose, CA 95120-6099, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Bianco
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Ming Te
authors.initials: MT
authors.lastname: Yeh
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Wright
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Butcher
authors.affiliation: Center for Quantitative Biology, School of Life Sciences, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Statistics, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Nielsen
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: raul.andino@ucsf.edu.
authors.forename: Raul
authors.initials: R
authors.lastname: Andino
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D019143:Evolution, Molecular; D005814:Genes, Viral; D056084:Genetic Fitness; D006801:Humans; D008957:Models, Genetic; D059645:Mutation Rate; D012327:RNA Virus Infections / Q000635:transmission / Q000821:virology; D012328:RNA Viruses / Q000235:genetics*