Low mutational load and high mutation rate variation in gut commensal bacteria

PLoS Biology
Ricardo RamiroIsabel Gordo

Abstract

Bacteria generally live in species-rich communities, such as the gut microbiota. Yet little is known about bacterial evolution in natural ecosystems. Here, we followed the long-term evolution of commensal Escherichia coli in the mouse gut. We observe the emergence of mutation rate polymorphism, ranging from wild-type levels to 1,000-fold higher. By combining experiments, whole-genome sequencing, and in silico simulations, we identify the molecular causes and explore the evolutionary conditions allowing these hypermutators to emerge and coexist within the microbiota. The hypermutator phenotype is caused by mutations in DNA polymerase III proofreading and catalytic subunits, which increase mutation rate by approximately 1,000-fold and stabilise hypermutator fitness, respectively. Strong mutation rate variation persists for >1,000 generations, with coexistence between lineages carrying 4 to >600 mutations. The in vivo molecular evolution pattern is consistent with fitness effects of deleterious mutations sd ≤ 10-4/generation, assuming a constant effect or exponentially distributed effects with a constant mean. Such effects are lower than typical in vitro estimates, leading to a low mutational load, an inference that is observed in...Continue Reading

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Citations

Aug 28, 2020·Genome Biology and Evolution·Rohan Maddamsetti, Nkrumah A Grant
Oct 6, 2020·Communicative & Integrative Biology·Hugo C BarretoIsabel Gordo
Jan 17, 2021·Antibiotics·Nikola Puvača, Rosa de Llanos Frutos
Jan 30, 2021·Nature Reviews. Gastroenterology & Hepatology·Jean-Paul MottaNathalie Vergnolle
Jan 12, 2021·Trends in Microbiology·Maria Rosa Domingo-Sananes, James O McInerney
Mar 5, 2021·Cell Host & Microbe·Bahtiyar YilmazAndrew J Macpherson
Jun 11, 2021·Cell Host & Microbe·Falk HildebrandPeer Bork
Aug 15, 2021·Nature Reviews. Genetics·Julie Perreau, Nancy A Moran
Jul 25, 2021·Genome Research·Ann-Marie Waldvogel, Markus Pfenninger
Nov 9, 2021·PLoS Genetics·Gemma G R MurrayLucy A Weinert

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Methods Mentioned

BETA
FACS
PCR

Software Mentioned

R
Ecocyc
R package nlme
PyMOL
EggNOG
SPAdes
FALCOR
BLAST
R package ggtree
breseq gdtools suite

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