100+ Years of Phase Variation – the Premier Bacterial Bet-Hedging Phenomenon

TY - JOUR

T1 - 100+ Years of Phase Variation – the Premier Bacterial Bet-Hedging Phenomenon

AU - Bayliss, Christopher D

AU - Clark, Jack

AU - Van Der Woude, Marjan

N1 - © 2025 The Authors

PY - 2025/2/27

Y1 - 2025/2/27

N2 - Stochastic, reversible, switches in expression of Salmonella flagella variants were first described by Andrewes in 1922. Termed phase variation (PV), subsequent research found that this phenomenon was widespread among bacterial species and controlled expression of major determinants of bacterial:host interactions. Under-lying mechanisms were not discovered until the 1970s/1980s but were found to encompass intrinsic aspects of DNA processes (i.e. DNA slippage and recombination) and DNA modifications (i.e. DNA methylation). Despite this long history, discoveries are on-going with expansions of the phase-variable repertoire into new organisms and novel insights into the functions of known loci and switching mechanisms. Some of these discoveries are somewhat controversial as the term ‘phase variation’ is being applied without addressing key aspects of the phenomenon such as whether mutations or epigenetic changes are reversible and generated prior to selection. Another ‘missing’ aspect of PV research is the impact of these adaptive switches in real-world situations. This review provides a perspective on the historical timeline of the discovery of PV, the current state-of-the-art, controversial aspects of classifying phase-variable loci and possible ‘missing’ real-world effects of this phenomenon.

AB - Stochastic, reversible, switches in expression of Salmonella flagella variants were first described by Andrewes in 1922. Termed phase variation (PV), subsequent research found that this phenomenon was widespread among bacterial species and controlled expression of major determinants of bacterial:host interactions. Under-lying mechanisms were not discovered until the 1970s/1980s but were found to encompass intrinsic aspects of DNA processes (i.e. DNA slippage and recombination) and DNA modifications (i.e. DNA methylation). Despite this long history, discoveries are on-going with expansions of the phase-variable repertoire into new organisms and novel insights into the functions of known loci and switching mechanisms. Some of these discoveries are somewhat controversial as the term ‘phase variation’ is being applied without addressing key aspects of the phenomenon such as whether mutations or epigenetic changes are reversible and generated prior to selection. Another ‘missing’ aspect of PV research is the impact of these adaptive switches in real-world situations. This review provides a perspective on the historical timeline of the discovery of PV, the current state-of-the-art, controversial aspects of classifying phase-variable loci and possible ‘missing’ real-world effects of this phenomenon.

KW - phase variation, microbiology, bacteria

UR - https://www.microbiologyresearch.org/docserver/fulltext/micro/171/2/mic001537.pdf?expires=1740995679&id=id&accname=guest&checksum=1310AD972E2DB2AD611175F9A8E1370F

U2 - 10.1099/mic.0.001537

DO - 10.1099/mic.0.001537

M3 - Review article

SN - 1350-0872

VL - 171

JO - Microbiology (Reading, England)

JF - Microbiology (Reading, England)

IS - 2

M1 - 001537

ER -