Precise Lineage Tracking Using Molecular Barcodes Demonstrates Fitness Trade-offs for Ivermectin Resistance in...

Area of Science:

• Evolutionary genetics
• Animal model systems
• Experimental evolution

Background:

• Environmental variation influences selection on genes.
• Barcoded lineage tracking is effective for measuring selection in microbial experimental evolution.
• Random genomic barcode integration in animals is challenging due to germline protection.

Purpose of the Study:

• To develop the first randomly inserted genomic-barcode experimental evolution animal model using Caenorhabditis elegans.
• To precisely measure the strength of selection on ivermectin resistance in C. elegans populations.
• To investigate the trade-offs associated with ivermectin resistance.

Main Methods:

• Utilized the TARDIS barcoding system in Caenorhabditis elegans.
• Created an experimental evolution model with random genomic barcode insertion.
• Varied ivermectin concentrations in liquid culture to control selection strength.
• Quantified barcode frequencies over time using deep sequencing to estimate lineage fitness.

Main Results:

• Demonstrated a high cost of ivermectin resistance at low drug concentrations.
• Observed that resistance becomes advantageous when ivermectin concentration exceeds 2nM.
• Identified a trade-off likely due to hindered development rates in resistant individuals.

Conclusions:

• Caenorhabditis elegans serves as a robust model for high-throughput fitness estimation in experimental evolution.
• This barcoding approach provides high-precision fitness estimates for studying evolutionary and economically important traits.
• The study highlights the environmental dependency of selection strength on specific genetic traits.