Loss-of-function mutations are main drivers of adaptations during short-term evolution

Area of Science:

• Evolutionary biology
• Genetics
• Molecular biology

Background:

• Gene inactivation mutations, including nonsense and frameshift mutations, are frequently observed in short-term experimental evolution and carcinogenesis.
• The adaptive significance of these gene loss-of-function mutations has been a subject of investigation.

Approach:

• A meta-analysis of 65 experiments was conducted using modified dN/dS statistics to assess mutation adaptiveness.
• Yeast (Saccharomyces cerevisiae) was employed as a model organism to empirically validate predictions regarding mutation adaptiveness.

Key Points:

• Meta-analysis indicated that nonsense mutations are adaptive across diverse experimental conditions.
• Empirical validation confirmed the adaptive nature of nonsense mutations.
• In yeast, fixed or highly frequent gene loss-of-function mutations were predominantly adaptive.

Conclusions:

• Gene inactivation mutations play a significant adaptive role in experimental evolution and carcinogenesis.
• Nonsense mutations are a key mechanism for adaptation in various evolutionary contexts.
• Loss-of-function mutations can be selectively advantageous, particularly in rapidly adapting populations like yeast.