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2015 ; 7
(7
): a018176
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The Origin of Mutants Under Selection: How Natural Selection Mimics Mutagenesis
(Adaptive Mutation)
#MMPMID26134316
Maisnier-Patin S
; Roth JR
Cold Spring Harb Perspect Biol
2015[Jul]; 7
(7
): a018176
PMID26134316
show ga
Selection detects mutants but does not cause mutations. Contrary to this dictum,
Cairns and Foster plated a leaky lac mutant of Escherichia coli on lactose medium
and saw revertant (Lac(+)) colonies accumulate with time above a nongrowing lawn.
This result suggested that bacteria might mutagenize their own genome when growth
is blocked. However, this conclusion is suspect in the light of recent evidence
that revertant colonies are initiated by preexisting cells with multiple copies
the conjugative F'lac plasmid, which carries the lac mutation. Some plated cells
have multiple copies of the simple F'lac plasmid. This provides sufficient LacZ
activity to support plasmid replication but not cell division. In nongrowing
cells, repeated plasmid replication increases the likelihood of a reversion
event. Reversion to lac(+) triggers exponential cell growth leading to a stable
Lac(+) revertant colony. In 10% of these plated cells, the high-copy plasmid
includes an internal tandem lac duplication, which provides even more LacZ
activity?sufficient to support slow growth and formation of an unstable Lac(+)
colony. Cells with multiple copies of the F'lac plasmid have an increased
mutation rate, because the plasmid encodes the error-prone (mutagenic) DNA
polymerase, DinB. Without DinB, unstable and stable Lac(+) revertant types form
in equal numbers and both types arise with no mutagenesis. Amplification and
selection are central to behavior of the Cairns-Foster system, whereas
mutagenesis is a system-specific side effect or artifact caused by
coamplification of dinB with lac. Study of this system has revealed several
broadly applicable principles. In all populations, gene duplications are frequent
stable genetic polymorphisms, common near-neutral mutant alleles can gain a
positive phenotype when amplified under selection, and natural selection can
operate without cell division when variability is generated by overreplication of
local genome subregions.