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Synonymous and nonsynonymous polymorphisms versus divergences in bacterial genomes.
Austin L Hughes1, Robert Friedman, Pierre Rivailler
1Department of Biological Sciences, University of South Carolina, USA.
Molecular Biology and Evolution
|August 1, 2008
Summary
The McDonald-Kreitman test may not reliably indicate positive selection. Purifying selection, not positive selection, likely drives bacterial evolution by removing harmful mutations.
Area of Science:
- Evolutionary biology
- Genomics
- Molecular evolution
Background:
- The McDonald-Kreitman test compares genetic variation within and between species to detect positive selection.
- The neutrality index (NI) is a key metric in this test, with values < 1 often interpreted as evidence of positive selection.
Purpose of the Study:
- To re-evaluate the interpretation of the neutrality index (NI) in bacterial evolution.
- To investigate the drivers of differences in NI across bacterial taxa.
Main Methods:
- Genome-wide comparison of polymorphism within 12 bacterial species.
- Analysis of divergence from an outgroup species.
- Correlation analysis between polymorphism levels, substitution rates, and NI.
Main Results:
- Substantial variation in NI was observed among bacterial taxa.
- Low levels of nonsynonymous polymorphism within species, not high substitution rates between species, predicted NI < 1.
- Genes with NI < 1 showed an excess of rare nonsynonymous polymorphisms, indicative of purifying selection.
Conclusions:
- High rates of nonsynonymous substitution between species likely result from purifying selection acting on slightly deleterious mutations within species.
- The findings challenge the common interpretation of the McDonald-Kreitman test as a sole indicator of positive Darwinian selection.
- Caution is advised when using the McDonald-Kreitman test and related statistics to infer positive selection in bacterial evolution.
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