phasevarion

Phasevarion is a regulatory concept in bacteria describing a regulon whose expression is governed by phase variation of a DNA methyltransferase, typically part of a restriction–modification system. When the methyltransferase is expressed, it methylates specific DNA motifs across the genome, leading to coordinated changes in the transcription of a large set of genes. The result is a phenotypic switch that generates diversity within a clonal population.

Mechanism-wise, the methyltransferase gene often contains repetitive DNA sequences that cause slipped-strand mispairing during replication. This can switch the gene ON or OFF or alter its specificity, changing the methylation pattern across the genome. Methylation can influence promoter activity, transcription factor binding, and DNA topology, thereby modulating the expression of many loci simultaneously and creating distinct transcriptional states.

Phasevarions have been described in several human pathogens, including Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, and Streptococcus pneumoniae. They contribute to virulence traits such as adhesion, invasion, immune evasion, and antimicrobial resistance, and can affect surface antigen expression. Because phasevarion states can vary within populations, they complicate vaccine design, diagnostics, and the interpretation of phenotypic assays.

Research into phasevarions highlights a role for epigenetic regulation in prokaryotes, showcasing how DNA methylation-dependent mechanisms can drive rapid and reversible phenotypic variation without changing the underlying DNA sequence. This understanding informs studies of pathogenesis and may guide the development of new therapeutic or preventive strategies.