497A Lecture 5

497A Lecture 5 - 1/21/11 1 Lecture 5 The Mechanisms of...

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Unformatted text preview: 1/21/11 1 Lecture 5 The Mechanisms of Viral Evolution I (largely RNA viruses) Studying Viral Evolution Three approaches: (i) Theoretical (mathematical modeling) (ii) Experimental ( in vitro studies of viruses like bacteriophages and VSV) (iii) Comparative (phylogenetic) Increasing in vivo experimental work on viral evolution 0.0 5 substitutions/site I I I I Thai strains 1980-19 4 Thai strains 19 0-20 2 Thai strains 1980-1983 Experimental evolution of equine influenza virus Quick Overview of Mechanisms of RNA Virus Evolution Mutation: - extremely high error rates in RNA viruses (~ 1 mutation per genome replication) Replication rates: - often extremely rapid in RNA viruses (~ 2.5 day generation time in HIV) Population sizes: - can be immense in RNA viruses (~ 10 8 to 10 10 in an HIV infected host, and many infected hosts) Natural selection: - variable power in RNA viruses and genes (although RNA viruses can adapt very quickly) Recombination/Reassortment: - variable rates among RNA viruses (although usually less frequent than other organisms) 1/21/11 2 Mutation Definitions Mutation (i) The biochemical process by which errors are made in gene sequences. Therefore, mutation rates refer to the intrinsic rate of biochemical error before the action of natural selection (so includes advantageous, neutral and deleterious mutations). (ii) Usually given as the number of errors (mutations) per genome, per replication. Substitution (i) The evolutionary process by which mutations are fixed in the population. Therefore, substitution rates refer to the number of accumulated changes after the action of natural selection (so excludes deleterious mutations) and is also influenced by the number of replications that have occurred. (ii) Usually given as the number of substitutions per site, per year. Comparative Rates of Evolutionary Change Bacteria & large DNA viruses: ~0.003 mutations per genome, per replication ~10-7 to 10-9 substitutions/site/year Eukaryotes: ~0.01 mutations per genome, per replication ~10-8 to 10-9 substitutions/site/year RNA viruses (and ssDNA viruses): ~1 mutation per genome, per replication* ~10-3 to 10-4 substitutions/site/year *Because RNA polymerase (RNA template) and reverse transcriptase (DNA template) have no proof-reading ability 1/21/11...
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497A Lecture 5 - 1/21/11 1 Lecture 5 The Mechanisms of...

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