Table 2

Definition of an AVG

QuestionAnswer
What is an AVG?An AVG is a gene whose expression in a pathogen is incompatible with the virulence of that pathogen. In the pathogen, an AVG is inactivated, deleted, or differentially regulated so that it cannot interfere with the virulence of that organism.
What is not an AVG?Suppressors. Certain genes, when inactivated under experimental conditions or determined to be nonfunctional in a limited number of natural isolates, can lead to an increase in virulence, a phenomenon commonly known as hypervirulence.
Genes not functional in the ancestral species. AVGs must have been present in the ancestral species before being inactivated or lost. As the ancestral strain or species may not always be available for study, the nearest related extant species may be acceptable for comparison. For example, Shigella species arose from an ancestral E. coli strain and Y. pestis diverged from Y. pseudotuberculosis. Pseudogene formation (and, consequently, AVG formation) in Shigella and Y. pestis may be studied by comparing their genomes or phenotypes to the corresponding extant species (E. coli and Y. pseudotuberculosis, respectively).
Genes that have undergone genetic decay due to close association with the known AVG(s). Only that gene which causes the antivirulence phenotype will be considered the AVG. Once that gene has been lost, other associated genes may become superfluous in the absence of a fully functional system and may therefore also decay. This process is part of reductive evolution.