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
Mechanisms of viral evolution
•
•
•
•
Mutation
Recombination
Reassortment
Selection
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.
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 (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!
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.
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.
Quasispecies, population size,
bottlenecks and fitness (Fig. 20.1)
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).
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.
• 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
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
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.
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.
L-A
M1
Dead
Cell
Toxin
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.
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.