Changing effective population size and the McDonald-Kreitman test

Area of Science:

• Evolutionary biology
• Population genetics
• Molecular evolution

Background:

• The McDonald-Kreitman test is a standard method for detecting positive selection.
• Artifactual signals of selection can arise under specific demographic and selective conditions.

Purpose of the Study:

• To investigate the conditions that generate artifactual evidence of adaptive amino acid substitution in the McDonald-Kreitman test.
• To determine the influence of effective population size and selection on synonymous codon use.

Main Methods:

• Simulations of population genetics models.
• Analysis of McDonald-Kreitman test statistics under varying demographic scenarios.
• Investigation of the role of slightly deleterious mutations and synonymous codon selection.

Main Results:

• Small increases in effective population size can generate artifactual evidence of positive selection, particularly when synonymous codon usage is not under selection.
• The removal of low-frequency polymorphisms exacerbates this artifactual signal.
• Selection acting on synonymous codon use can restrict the conditions under which artifactual evidence of adaptive evolution is observed.

Conclusions:

• Demographic changes, specifically increased effective population size, can mislead interpretations of the McDonald-Kreitman test.
• Synonymous codon selection plays a crucial role in mitigating false positives for adaptive evolution.
• Careful consideration of population history and selective pressures is necessary when interpreting McDonald-Kreitman test results.