Virus Evolution. Lecture 6. Chapter 20, pp. 759 – 777.

1. Virus Evolution.Lecture 6. Chapter 20, pp. 759 – 777. Basic point: Virus evolution is fast Fast generation time High rates of fecundity High rates of mutation

2. Mechanisms of viral evolution • Mutation • Recombination • Reassortment • Selection

3. Virus-infected cells produce large numbers of progeny (fecundity) • Infection of a single cell by poliovirus can yield up to 104 viral particles. • In a person, up to 109 – 1011 particles can be produced per day • Enough to infect every person on the planet.

5. High mutation rates: genome replication is inaccurate • Evolution requires mutation • Mutations occur when nucleic acids are copied (i.e. genome replication) • Baseline chemical mutation rate (keto to enol tautamarization of thymidine) = 10-4 • Error rate of human DNA polymerase is approximately 10-9 (3 mutations per replication of the human genome). • Error correction machinery lowers this to 10-11 • Virus RNA and DNA polymerases are much more error prone • RNA dependent RNA pol error rates: 10-4 – 10-5 • DNA polymerases: 10-6 – 10-7

6. Some numbers Given • An RNA virus with a genome of 10 kb (i.e. 104 kb) • RDRP error rate of 10-5 • 10-5/104 = 10-1 = 1 in 10 progeny genomes will contain a mutation. • If 109 viral particles produced in a person per day, then 108 mutant progeny are being produced in that one individual each day of infection!

7. Quasispecies, error threshold, bottlenecks and fitness • Quasispecies: Virus populations as • dynamic distributions of nonidentical • but related replicons. • The error threshold: Too much mutation can be lead to loss of vital information, while too little mutation can lead to host defenses overcoming the virus. Error threshold is a mathematical parameter that measures the complexity of the information that must be maintained to ensure survival of the population. The greatest fitness is when mutation rates approach the error threshold. • Genetic drift: slow accumulation of mutations in a population. Due to constant selective pressure in a single host species. • Genetic shift: a major genetic change caused by mixing of genomes derived from two distinct populations of viruses, e.g. viruses that infect two different species.

8. More Terms • Genetic information exchange: Genetic information is exchanged by recombination of genome segments. Infection of a cell by two different viruses can result in exchange of genetic information, resulting in production of mixed progeny. • Genetic bottleneck: extreme selective pressure on a small population. Results in loss of diversity and accumulation of non-selected mutations. • Fitness: the replicative adaptability of an organism to its environment. Fitness is influenced by all of the above.

9. Quasispecies, population size, bottlenecks and fitness (Fig. 20.1)

10. Two general pathways for virus evolution Co-evolution with host • Advantage: prosperous host = prosperous virus • Disadvantage: virus shares same fate as host. Genetic bottleneck events can be fatal. • Typically used by DNA viruses Infection of multiple host species. • Advantage: if one host species is compromised, virus can replicate in another • Disadvantage: cannot optimize for any one situation. • Typically used by RNA viruses

11. The origin of viruses (Table 20.3). 1. Regressive evolution (parasitism) • Viruses degenerated from previously independent life forms • Lost many functions • Retain only what they needed for parasitic lifestyle 2. Cellular origins • Viruses derived from subcellular functional assemblies of macromolecules that gained the capacity to move from cell to cell. 3. Independent entities • Evolution on course parallel to that of cellular organisms. • Evolved from primitive, pre-biotic self-replicating molecules.

12. Problem: no fossil record. • Solution: Genomes as the fossil record. • Relationships among different viral genomes provide insight into virus origins. This is the basis of molecular taxonomy. Fig. 20.2

13. Co-evolution with host populations. • Association of a given viral genome sequence with a particular host group. • e.g. different papillomaviruses subtypes are more prevalent in different human populations. • Can use viruses to trace human origins

14. Co-evolution and fitness • Highly virulent virus will kill the host too soon • Too exposed and the host will kill it.  Viruses and hosts tend to co-evolve toward symbiotic or at least mutualistic relationships.

15. L-A M1 Dead Cell Toxin Co-evolution and fitness • Example: the yeast killer virus. • L-A is a metabolic parasite of the host • M is a parasite of L-A • However, M confers a selective advantage on host. • Host tolerates L-A to maintain M. • L-A tolerates M to stay in good graces with host.

16. Evolution is both constrained and driven by the fundamental properties of viruses • A virus clade can be < 10% divergent • Despite lots of sequence diversity, viral populations maintain stable master or consensus sequences. • Diversity limited to ability to function within certain constraints. These include: • Particle geometry: eg. Icosahedral capsids limit genome size by limiting volume. • Genomes composed of nucleic acids limits solutions to replication of decoding of viral information. • Requirement for interactions with host cell machinery. • Requirements for interactions within the host organism.

17. Evolution of new viruses. • Even within constraints, the potential for new mutations is huge. • e.g. fully ½ of all bases in an RNA genome can be mutated without killing the virus. • For a virus of 104 kb,  45000 possible sequence permutations due to simple mutation alone. • Even more with recombination. • By contrast, the visible universe contains 4135 atoms. • Conclusion: virus evolution is inescapable and relentless.