Effective polyploidy causes phenotypic delay and influences bacterial evolvability

PLoS Biology
Lei SunSebastian Bonhoeffer

Abstract

Whether mutations in bacteria exhibit a noticeable delay before expressing their corresponding mutant phenotype was discussed intensively in the 1940s to 1950s, but the discussion eventually waned for lack of supportive evidence and perceived incompatibility with observed mutant distributions in fluctuation tests. Phenotypic delay in bacteria is widely assumed to be negligible, despite the lack of direct evidence. Here, we revisited the question using recombineering to introduce antibiotic resistance mutations into E. coli at defined time points and then tracking expression of the corresponding mutant phenotype over time. Contrary to previous assumptions, we found a substantial median phenotypic delay of three to four generations. We provided evidence that the primary source of this delay is multifork replication causing cells to be effectively polyploid, whereby wild-type gene copies transiently mask the phenotype of recessive mutant gene copies in the same cell. Using modeling and simulation methods, we explored the consequences of effective polyploidy for mutation rate estimation by fluctuation tests and sequencing-based methods. For recessive mutations, despite the substantial phenotypic delay, the per-copy or per-genome mu...Continue Reading

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Citations

Mar 21, 2020·Biochemical Society Transactions·Maxence S Vincent, Stephan Uphoff
May 30, 2020·PLoS Computational Biology·Martín Carballo-PachecoBartlomiej Waclaw
May 29, 2020·Genetics·Mario Santer, Hildegard Uecker
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Jun 17, 2020·Trends in Microbiology·Jake L WeissmanPhilip L F Johnson
Mar 8, 2021·Genome Biology and Evolution·Esther R Angert

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Methods Mentioned

BETA
genetic modification
protein folding

Software Mentioned

R packages
FALCOR
MATLAB
R

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