Virus Evolution
Chapter 20, pp. 759 – 777.
Lecture 6. BSCI437
Basic point: Virus evolution is fast due to
Fast generation time
High rates of fecundity
High rates of mutation
Mechanisms of viral evolution
Mutation
Recombination
Reassortment
Selection
Virus-infected cells produce large numbers of progeny (fecundity) See table 20.1.
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.
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
Some numbers.
Given
 An RNA virus with a genome of 10 kb x RDRP error rate of 10-5
 = 1 mutant in 1 position for every 10 virions produced.
 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!
Quasispecies, error threshold, bottlenecks and fitness (Fig. 20.1)
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.
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.
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
The origin of viruses (Table 20.3).
Regressive evolution (parasitism)
Viruses degenerated from previously independent life forms
Lost many functions
Retain only what they needed for parasitic lifestyle
Cellular origins
Viruses derived from subcellular functional assemblies of macromolecules
that gained the capacity to move from cell to cell.
Independent entities
Evolution on course parallel to that of cellular organisms.
Evolved from primitive, pre-biotic self-replicating molecules.
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. See fig. 20.2.
Co-evolution with host populations.
Association of a given viral genome sequence with a particular host group.
eg.different papillomaviruses subtypes are more prevalent in different human
populations.
Can use viruses to trace human origins
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.
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.
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 caplids limit genome size by limiting volume.
Genomes composed of nucleic acids limits limits solutions to replication of decoding of
viral information.
Requirement for interactions with host cell machinery.
Requirements for interactions within the host.
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.