Idiosyncratic evolvability among single-point ribosomal mutants towards multi-aminoglycoside resistance

Area of Science:

• Microbiology
• Evolutionary Biology
• Genetics

Background:

• Mutations impact organism fitness and future adaptation capacity (evolvability).
• A common pattern shows evolvability decreases as genotype fitness increases (rule of declining adaptability).
• This decline is often attributed to epistasis rather than mutation differences.

Purpose of the Study:

• Investigate how rpsL mutations in Escherichia coli affect adaptation to secondary aminoglycosides.
• Determine if initial genotype fitness influences the rate and effect size of beneficial mutations.
• Explore the genetic basis of adaptation and resistance development.

Main Methods:

• Utilized Escherichia coli with rpsL point mutations conferring streptomycin resistance.
• Assessed adaptation to secondary aminoglycosides.
• Performed genome sequencing to identify genetic targets of adaptation.

Main Results:

• Observed a modified rule of declining adaptability: fitter genotypes had higher beneficial mutation rates but smaller effect sizes.
• Identified ribosome and electron transport chain as key adaptation targets.
• Second mutations often conferred cross-resistance and sometimes restored fitness.

Conclusions:

• Fitter genotypes adapt differently, with faster but smaller evolutionary steps.
• Some mutations lead to evolutionary dead-ends, unable to adapt to secondary aminoglycosides.
• Understanding these patterns can inform strategies against multidrug resistance and for evolutionary robustness.