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Updated: May 23, 2026
09:40
Novel Sequence Discovery by Subtractive Genomics
Published on: January 25, 2019
Looking for Darwin in genomic sequences--validity and success of statistical methods
Weiwei Zhai1, Rasmus Nielsen, Nick Goldman
1Center for Computational Biology and Laboratory of Disease Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China.
Molecular Biology and Evolution
|April 12, 2012
Summary
Codon substitution models are valuable for detecting positive Darwinian selection in protein evolution. Contrary to recent claims, these models, when properly applied, accurately reflect evolutionary pressures, not just random fluctuations.
Area of Science:
- Evolutionary biology
- Genomics
- Molecular evolution
Background:
- Codon substitution models are standard for assessing protein evolution by comparing synonymous and nonsynonymous substitution rates.
- Hughes and colleagues have recently challenged the validity of codon-based likelihood-ratio tests (LRTs), citing logical flaws and inability to account for random fluctuations.
Purpose of the Study:
- To reanalyze data previously used to critique codon-based LRTs.
- To address criticisms regarding the reliability of codon-based tests for detecting positive Darwinian selection.
Main Methods:
- Reanalysis of gene family data from Friedman and Hughes (2007).
- Application of site-based LRTs to human and mouse paralogues.
- Statistical examination of factors influencing test outcomes, including sequence length and d(N)/d(S) ratio.
Main Results:
- Contrary to Friedman and Hughes, test results were found to correlate with sequence length and average d(N)/d(S) ratio.
- Criticisms by Hughes were identified as stemming from misunderstandings of codon models and statistical errors.
Conclusions:
- Codon-based tests remain robust and useful tools for comparative genomic analysis.
- The validity of codon-based LRTs for detecting positive selection is reaffirmed.
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