Viral genome evolution

Viral genomes are the fastest evolving entities in biology, mainly because of their short replication time and the large quantity of offspring released per cell infected. Evolution occurs by several mechanisms: Random mutation, recombination, reassortment, gene amplification/reduction; and results in quasispecies and defective interfering genomes

Random mutation [genetic drift]:

Virus genomes display a higher mutation rate than cellular organisms. Indeed viral polymerases have a higher mutation rate than cellular polymerases, in particular RNA dependent RNA polymerases. Moreover virus replication process often do not support cellular reparation mecanisms based on double strand repair. This high mutation rate produces often more deficient than infectious genomes, but it allows to evolve rapidly through natural selection.

The mutation rate represents the number of mutations per site per replication. It is different from the substitution rate which is an observed number of mutations fixed in the genome per site per year. Mutation rate and substitution rate differ due to selection pressure .


Recombination by crossing over [genetic shift]:

Virus genome can evolve by recombination. There is two kind of recombination: self recombination and recombination with host.
Self recombination occurs when two viral genomes recombine by homologous crossing over. This happens for DNA viruses and is very common in prokaryotic viruses, but also for RNA viruses or retroviruses. These recombination events can be of evolutionary advantage for the virus when it helps to evade host immune defenses, for example by changing surface protein antigenicity.
Recombination with host or other organism occurs when a viral genome recombine to acquire sequences from another organism. Natural selection can retain acquired sequence if it gives an evolutionary advantage to the virus and mutations can modify its original functions. This event is common in large dsDNA viruses, some eukaryotic viruses even acquired many genes from bacteria.


Segment reassortment [genetic shift]:

Reassortment occurs event when two similar segmented viruses exchange part of their genomes during a cell co-infection. This event occurs in all segmented viruses. It is particularly studied for Influenza virus, since reassortment is the major event giving rise to new flu pandemics.


Gene amplification/reduction

In poxviridae, gene copy number amplification provides an immediate fitness advantage and additional gene copies for potential beneficial mutations. After acquisition of a beneficial mutation, virus genomes are selected that retain advantageous point mutations without the gene expansion, leading to contractions down to a single gene copy.

Consequences of viral evolution:

-Viral quasispecies: The fast and flexible evolution of RNA virus genomes creates population of viruses which are all different, called Viral quasispecies because a single sequence cannot describe accurately the viral population in a single host or even in cell culture.

-Defective interfering virus: Defective interfering viruses (DIs) arise through deletion, rearrangement, or recombination of a competent viral genome. DIs are related to satellite virus, but unlike them they are not conserved by natural selection, they appear and disappear. DIs compete with the viral genome for replication and/or encapsidation factors and therefore tend to attenuate the virus and trigger host antiviral defenses. These defective genome are accumulating in cell culture, where innate antiviral defense is often defective, therefore removing the negative selection of DIs. For example Sendai virus is used in cell culture to induce interferon, eventhough if wild type Sendai is shutting off IFN production. Actually Sendai grown in cell culture is full of DIs, which are very potent to induce innate immunity.