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

Area of Science:

• Microbial Ecology
• Evolutionary Biology
• Genetics

Background:

• Bacteria inhabit complex communities like the gut microbiota.
• Bacterial evolution within natural ecosystems remains poorly understood.

Purpose of the Study:

• To investigate the long-term evolution of commensal Escherichia coli in the mouse gut.
• To identify the molecular causes and evolutionary conditions for hypermutator emergence and coexistence.

Main Methods:

• Long-term evolution experiments with Escherichia coli in mouse guts.
• Whole-genome sequencing to track mutations.
• In silico simulations to model evolutionary dynamics.

Main Results:

• Observed emergence of mutation rate polymorphism, with some strains becoming 1,000-fold hypermutators.
• Identified mutations in DNA polymerase III subunits as the cause of hypermutability.
• Demonstrated coexistence of hypermutator and wild-type lineages for over 1,000 generations.
• Found that deleterious mutations have low fitness effects in vivo, leading to low mutational load.
• Observed beneficial mutations that do not reach fixation, suggesting alternative evolutionary dynamics.

Conclusions:

• Gut bacterial evolution is characterized by mutation rate polymorphism and the coexistence of diverse lineages.
• Evolutionary mechanisms beyond simple positive selection, like partial sweeps and hitchhiking, maintain genetic diversity.
• These findings explain genetic polymorphism patterns observed in human gut microbiota metagenomics studies.