Selection for robustness in mutagenized RNA viruses.

Area of Science:

• Evolutionary biology
• Virology
• Genetics

Background:

• Mutational robustness, the ability of a phenotype to remain constant despite mutations, is crucial for organismal survival.
• The direct selection for mutational robustness remains a contentious topic in evolutionary theory.
• Previous theoretical and in silico studies suggested that robustness could be advantageous at high mutation rates.

Purpose of the Study:

• To experimentally test the hypothesis that natural selection can directly favor mutational robustness, termed "survival of the flattest."
• To investigate the role of mutational robustness in viral population dynamics and resistance.
• To explore viral resistance mechanisms against lethal mutagenesis treatments.

Main Methods:

• Utilizing two distinct populations of the vesicular stomatitis RNA virus for experimental evolution.
• Characterizing fitness distributions and genetic variability within each viral population.
• Conducting competition assays under standard conditions and in the presence of chemical mutagens.

Main Results:

• One viral population exhibited a higher replication rate, while the other demonstrated greater mutational robustness.
• The faster-replicating virus initially outcompeted the robust population in standard assays.
• The robust viral population outperformed the faster replicator when exposed to chemical mutagens, indicating a survival advantage.

Conclusions:

• Experimental evidence supports the direct selection for mutational robustness in RNA viruses.
• The study validates the "survival of the flattest" hypothesis under specific conditions.
• Mutational robustness represents a novel viral resistance mechanism against lethal mutagenesis therapies.