Coronavirus Evolution

• Evolution Speed
• Terminology
• Evolution Occurrence and Mechanisms
• Evolution Variations across the Genome
  • Effects of Genome Evolution
  • Determinants of Evolutionary Rate
• Observed Evolution
• References

Evolution Speed

The genetic evolution of coronaviruses is fast compared to other forms of life because:

• a short average generation-time (only a few hours [to be confirmed])
• Genome is encoded in single stranded RNA.
  • RNA mutates more than DNA and is more difficult to correct
  • single stranded genomes are less stable than double stranded
  • properties of their genome copying:
    • single stranded RNA is copied by RNA-dependent RNA polymerase, which yields a higher rate of random point errors (mutations) compared to DNA polymerases
    • a homologous recombination mechanism [Woo et al.] , more refs coming]
• A large overall populations size = (within host population) * (number of infected hosts)
  • large population size within hosts.
  • the number of infected hosts can be large (for Sars-CoV-2)

    This ignores the transmission bottleneck which is usually only a couple of viruses. Therefore if SARS-CoV-2 frequently changes hosts the effective population size is much lower.

• Coronaviruses have large genomes (in comparison to other RNA viruses or messenger RNAs) which both back the recombination and encode complex proteins. The coronavirus RNA genome is among the largest strands of RNA occurring on todays earth, possibly even the largest [to check].

Terminology

in work and subject to changes

Virus Lineage

A lineage of viruses denotes all viruses originating from a single virus. In the case of recombination, the recombined virus belongs to both lineages.

• The term lineage is independent of mutations and just denotes a parent offspring relationship.

Coronavirus Species

A coronavirus species denotes a collection of lineages of coronaviruses which readily undergo recombination.

• The above definition is analog to the definition of species for animals with sexual recombination, where a species denotes a set of lineages with can recombine.
• The above definition means the viruses draw from the same gene pool.

Traditionally virus species are defined on antibody binding [to confirm and cite].

Virus Variant

A virus variant is a collection of virus lineages which belong to the same species but differ in their behavior.

Virus Strain

A virus variant is a collection of virus lineages where the members share the behavior but not necessarily the structure or sequence.

• Members of a variant may differ in a couple of point mutations at the amino acid level which don’t change the behavior.

Evolution Occurrence and Mechanisms

• Spontaneous Mutation
• Mutation upon Duplication
• Recombination (template switch)

Evolution Variations across the Genome

This section is written generally and valid for most life forms

Effects of Genome Evolution

Change the Evolutionary Stability

Changing the RNA or protein structure even without immediate effects on the function can influence future mutations. This can yield more mutative or more stable progeny.

+/-:

• In a changing environment with relaxed survival constraints, a mutative state is advantageous regarding the change of functions.
• Exposed to immune responses targeting molecular patterns, change of molecular appearance is beneficial.

Change the Functioning

Change the function which is beneficial if the previous functioning was suboptimal and the new function does better.

+/-: Most mutations do not improve the function. However if they do the advantage can be significant.

• If the life-form is not well adapted to the environment, function improvement upon function change is more likely.
• If the life-form is in an environment with relaxed fitness constraints, delirious mutations are better tolerated.

Change the Molecular Appearance

Changing the appearance can yield escape from immune system recognition.

+: Escaping the immune system is often beneficial or even required for a virus lineage to survive.

Determinants of Evolutionary Rate

in raw work and incomplete

Immune Evasion Drive

• Exposure: Internal proteins of viruses are more difficult to target for the immune system, therefore the corresponding genes have less evolutionary drive to mutate:
  • Virion Phase: Antibodies can target the external proteins of virions.
  • Metabolic Phase: Cells target proteins present via MHC 1, and possibly antibodies [to check and cite]. Some cells take up antibodies these antibodies can bind the virions during the metabolic phase.
• Expression Level: Proteins with low expression levels: The immune system learning system comes more in contact with frequent proteins and thus learns them more likely.
  • For coronaviruses (for most other viruses too) the non structural proteins have much lower expression levels than the structural proteins.
  • The share of proteins mass is as follows: 1. N protein, 2. S protein, 3. E Protein, 4. M Membrane Protein [to finish, check and cite]

Functional Drive

• Stabilizing = Conserved Functions: Functional units of proteins with virus intrinsic functions:
  • The replication mechanism of coronaviruses is well conserved and thus the proteins involved e.g. functional parts of the RNA-dependent RNA polymerase protein (RdRP) [to check and cite].
• Mutative = Functions to Optimize:
  • The receptor binding needs to be optimized upon a species jump.
  • The spike protein is a key determinant of the tropism, thus a tropism change is often associated with changes in the spike.
  • Shutting down cellular immune responses needs to be adapted upon a species jump and sometimes upon tropism change if the new target cells have different intracellular immunity. E.g. the NSP6 protein is
• No Functional Drive = Functionless structures:
  • E.g. the N terminal part of the spike of SARS-CoV-1/2 has no known function.

Observed Evolution

• Bovine coronaviruses spread from cattle to many ungulates both domestic and wild [to cite].
• In cell cultures coronavirus can adapt within a couple of generations. E.g.
  • they can adapt such that the virions tolerate high temperature (55 degrees) better Laude.
• SARS-CoV-2 jumps to domestic animals and adapts.

References

Woo

Woo, P. C., Lau, S. K., Huang, Y., Yuen, K. Y. (2009). Coronavirus diversity, phylogeny and interspecies jumping. Experimental biology and medicine (Maywood, N.J.), 234(10), 1117–1127. https://doi.org/10.3181/0903-MR-94