1. Ecology and Evolutionary Biology of Viruses

2. SOME CONSEQUENCES AND EFFECTS OF VIRUS INFECTION Like other life forms, viruses promote the propagation of their own kind Like other life forms, viruses evolve in response to selection pressure Viruses are major factors in promoting the evolution of higher organisms Viruses help control populations of their hosts, including humans

3. Host properties influence the virus types found in that host group Vertebrates have broad range of viruses Plants have mostly small RNA viruses Fungi have mostly dsRNA viruses Single-celled organisms have mostly large dsDNA viruses

4. Overview of Virus Properties Animal –RNA – 5-30 kb –DNA: 5-350 kb –Many enveloped –Range of complexity –Range of morphologies –Some divided genomes Prokaryote –RNA – 5-8 kb – DNA – 10-200 kb –Few enveloped –Range of complexity –Range of morphologies –Few divided genomes True Fungi – RNA – 2.5-28 kb –DNA – none –Enveloped ones have no capsid –Little genome complexity –Little morphological complexity –Some divided genomes Plant – RNA – 0.3-28 kb –DNA – 3-10 kb –Few enveloped –Little genome complexity –Little morphological complexity –Many divided genomes Lower eukaryote –RNA – 5-10 kb – DNA – 180-1200 kb –Internal envelope –Range of complexity –Range of morphologies –No divided genomes

5. Virus transmission Animal viruses are transmitted through air, through wounds, through orifices, or by vectors Most plant viruses are transmitted by vectors, especially homopterous insects Most fungal viruses are transmitted horizontally only by hyphal fusion Bacterial viruses are transmitted by attachment of free virus to bacterial cell walls or pili; injection of nucleic acid How do these transmission modes affect their ecology and evolutionary biology?

6. Virus Evolution Viruses origins are unknown Theories of virus origin: –Regressive evolution: viruses degenerated from previously independent life forms, lost many functions required by cellular organisms –Cellular origins: viruses assembled from cellular components into independent entities capable of moving cell-to-cell and, later, gaining ability capacity for transmission –Independent entities: viruses evolved independently and in parallel with complex organisms from self-replicating molecules in the primordial RNA world These theories are not mutually exclusive – different virus lineages may have different origins

7. Virus evolution Virus evolution is contemporary and observable Large numbers of progeny contribute to potential high rate of evolution of viruses Mutation rate is higher for RNA than for DNA Evolution rate does not necessarily reflect mutation rate Mutation rate for a particular virus may be different in different tissues Different parts of viral genomes evolve at different rates Ability to generate large amounts of sequence data has greatly enhanced ability to study evolution

8. Sequence variation during virus replication Intrinsic error rates of polymerases are difficult to quantify DNA polymerase has proof-reading capability; intrinsic error rate is low, usually ~ 10 -6 to 10 -5 RNA polymerase has no proof-reading capability; intrinsic error rate is high, usually ~ 10 -4 to 10 -3 Error rates may be different in different genome regions, e.g., “hotspots” Homologous or non-homologous recombination may occur in RNA or DNA viruses Change of templates is referred to as copy choice

9. Means of RNA virus evolution Minor replication error (substitution, single base change) – no error correction by RdRp Major replication error (deletion) Intragenomic gene duplication Intergenomic recombination –gene duplication –acquisition of additional genes –coding sequence or noncoding sequence substitution Virus evolution may be accelerated by co- infection

10. Positive-strand RNA virus evolution Positive-strand RNA viruses evolve rapidly; only important functional domains are conserved RNA viruses are made up of a limited number of building blocks; only RdRp is required and is the ultimate basis of rational phylogenies Evolution of RNA viruses involves conservation of required genes and recombination/shuffling of gene blocks Widespread recombination of a relatively small number of genes makes it impossible to generate single phylogenetic trees (reticulate evolution) Basic RNA virus replication machinery likely evolved more than once

11. Positive-strand RNA virus evolution A. Organization of conserved replication-associated genes of major groups of positive-sense RNA viruses; B. Phylogenetic reconstruction of selected alphaviruses based on RdRp gene. From your text: Flint et al., 2004

12. * * * * * OMV4 (2.6 kb) CMV1/NB631 (2.7 kb) SNV/23S (2.9 kb) Qβ (3.6 kb) TBSV (4.8 kb) PEMV (4.2 kb) DRV (4.1 kb) * * Cyto (Cyto) Mito Cyto Mito Plant Bacterium Fungus Yeast Plant Fungus Yes No VirusLocationHostCapsid? Viruses closely related to RNA bacteriophages (Leviviridae) * = core RNA-dependent RNA polymerase domain = capsid protein gene = stop codon position

13. Genome organizations of negative-sense RNA viruses, and homologies among genes From text: Flint et al., 2004

14. Mechanisms of recombination of viral RNAs Left: Generalized viral RNA recombination. Bottom: Three classes of intergenomic RNA recombination: 1) Requiring substantial base pairing but no identifiable RNA secondary structures or regulatory elements; 2) Occurring in association with identifiable RNA,structures or regulatory elements, but not requiring substantial base pairing; 3) A combination of 1 and 2. From your text: Flint et al., 2004

15. Variation among viral sequences The term “quasi species” is used predominately for RNA viruses Because of absence of proofreading, many variants are found in an RNA virus population; the “quasi- species cloud” is the mutant spectrum derived from the dominant master copy A genetic bottleneck occurs when a virus population is constrained, resulting in loss of diversity – can be because of: –vector constraints –host defense constraints A small founder population coming through a genetic bottleneck may give rise to a skewed population

16. Viral quasispecies, population size, bottlenecks, and fitness From your text: Flint et al., 2004

17. From Drake & Holland, 1999, PNAS 96:13909 Intrinsic mutation rates among RNA viruses vary In the absence of selection, spontaneous mutation rates of different viral RNA polymerases are high, and vary by ~10 fold.