On the stability of sequences inserted into viral genomes

Willemsen, Anouk; Zwart, Mark P

• Large genomes that are readily engineered and also highly plastic, as exemplified by the 'genome accordion' in poxviruses • Small insertions can be stable, but larger insertion are rapidly lost • Classic studies with phages exemplify how lower limits to the size of packaged genomes can be used to increase insertion stability II: The inverted terminal repeats of vaccinia virus undergo rapid changes in size due to unequal crossover events leading to stable and unstable forms (Moss, Winters, and Cooper 1981) . The diversity in this region is needed for immune evasion and for the colonization of novel hosts and appears to be mainly regulated by recombination events. However, other processes such as mutation leading to accelerated rates of recombination cannot be ruled out. Poxviruses, such as vaccinia, virus are classified as nucleocytoplasmic large DNA viruses (NCLDVs). These viruses have larger than average genome sizes and the more recently discovered giant viruses are also classified as such. The NCLDVs appear to have undergone a dynamic evolution where gene gain and loss events go in parallel with host-switches between animal and protist hosts (Koonin and Yutin 2018) . Interestingly, the phylogenomic reconstructions performed by Koonin and Yutin (2018) suggest that giant viruses (for which the host range appears to be restricted to protists) have evolved from simpler viruses (infecting animals) on many independent occasions. This again suggests that the host plays an important role in genome stability where in animals the pressure for smaller virus genomes is stronger than in protists (Koonin and Yutin 2018) .