Environmental changes bridge evolutionary valleys.

Area of Science:

• Molecular evolution
• Biochemistry
• Genetics

Background:

• Evolutionary pathways typically follow increasing fitness.
• Crossing fitness valleys remains a challenge in molecular evolution.
• Environmental changes may alter fitness landscapes, enabling valley crossing.

Purpose of the Study:

• To experimentally test if environmental changes can facilitate crossing fitness valleys.
• To investigate evolutionary strategies for generating superior alleles in antibiotic resistance genes.
• To understand the role of negative selection in accessing novel evolutionary trajectories.

Main Methods:

• Experimental evolution using the TEM-15 β-lactamase gene.
• Comparison of four evolutionary strategies under varying environmental conditions.
• Analysis of evolutionary pathways and mutational epistasis for high-fitness alleles.

Main Results:

• A strategy involving initial negative selection yielded superior antibiotic resistance alleles.
• An initially deleterious mutation was identified as crucial for accessing new sequence space.
• This key mutation exhibited positive epistasis with subsequent neutral or beneficial mutations.

Conclusions:

• Environmental changes and negative selection can provide access to previously inaccessible fitness peaks.
• This approach has significant implications for understanding natural evolution and for directed evolution applications.
• Deleterious mutations can act as gateways to novel evolutionary pathways.