The McDonald-Kreitman test and slightly deleterious mutations

Area of Science:

• Evolutionary biology
• Population genetics

Background:

• Estimating adaptive evolution relies on McDonald and Kreitman analyses of polymorphisms and substitutions.
• Segregation of slightly deleterious mutations introduces downward bias in these estimates.

Purpose of the Study:

• To theoretically investigate the performance of removing low-frequency polymorphisms to mitigate bias in adaptive evolution estimates.
• To assess the reliability of this method under varying conditions of adaptive evolution and deleterious mutation effects.

Main Methods:

• Theoretical analysis of bias in McDonald and Kreitman-type analyses.
• Modeling the impact of removing low-frequency polymorphisms on adaptive evolution estimates.

Main Results:

• Removing low-frequency polymorphisms reduces bias but consistently results in downwardly biased estimates.
• Detection of adaptive evolution may be hindered even when it is prevalent.
• The method is only satisfactory under high adaptive evolution rates and leptokurtic deleterious mutation distributions.

Conclusions:

• Current methods may substantially underestimate adaptive evolution in humans, bacteria, and Drosophila.
• Adaptive evolution could be more prevalent than previously detected, even in humans (>8%).
• Refined methodologies are needed to accurately detect adaptive evolution when slightly deleterious mutations are present.