In genetics, the K_a/K_s ratio (or ω, dN/dS), is the ratio of the rate of non-synonymous substitutions (K_a) to the rate of synonymous substitutions (K_s), which can be used as an indicator of selective pressure acting on a protein-coding gene. Comparisons of homologous genes with a high K_a/K_s ratio are usually said to be evolving under positive selection.

Methods for estimating K_a and K_s can be classified into two groups: approximate methods and maximum-likelihood methods. Approximate methods involve three basic steps:

1. counting the number of synonymous and nonsynonymous sites
2. counting the number of synonymous and nonsynonymous substitutions, and
3. correcting for multiple substitutions.

The maximum-likelihood approach uses the probability theory to finish all three steps in one go.^[1]

[edit] Limitations of application

Although Ka/Ks is a good indicator of selective pressure at the sequence level, evolutionary change is often down to the change in amount and position of protein expressed by its gene, which is instead marked by a change in the regulatory region of genes, rather than their specific protein coding regions. Also, some genes often only partly show positive selection. Ka/Ks analysis is unequipped to consider such aspects.

Another issue is that heterogeneity within a gene can make a result hard to interpret. For example, if Ka/Ks = 1, it could be due to relaxed selection, or to a chimera of positive and purifying selection at the locus. A solution to this limitation would be to apply Ka/Ks analysis across many species at individual codons.

[edit] References

• Li WH, Wu CI, Luo CC. 1985. A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes. Mol Biol Evol 2(2):150-174.
• Nei M, Gojobori T. 1986. Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 3(5):418-426.
• Li WH. 1993. Unbiased estimation of the Rates of synonymous and nonsynonymous substitution. J Mol Evol 36:96-99.
• Pamilo P, Bianchi NO.1993. Evolution of the Zfx and Zfy genes: rates and interdependence between the genes. Mol Biol Evol 10(2):271-281.
• Muse SV, Gaut BS: A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to the chloroplast genome. Mol Biol Evol 1994, 11(5):715-724.
• Goldman N, Yang Z: A codon-based model of nucleotide substitution for protein-coding DNA sequences. Mol Biol Evol 1994, 11(5):725-736.
• Comeron JM: A method for estimating the numbers of synonymous and nonsynonymous substitutions per site. J Mol Evol 1995, 41:1152-1159.
• Ina Y: New methods for estimating the numbers of synonymous and nonsynonymous substitutions. J Mol Evol 1995, 40:190-226.
• Yang Z: PAML: a program package for phylogenetic analysis by maximum likelihood. CABIOS 1997, 13:555-556.
• Yang Z, Nielsen R: Estimating Synonymous and Nonsynonymous Substitution Rates Under Realistic Evolutionary Models. Mol Biol Evol 2000, 17(1):32-43.
• Zhang Z, Li J, Yu J: Computing Ka and Ks with a consideration of unequal transitional substitutions. BMC evolutionary biology 2006, 6:44.
• Zhang Z, Li J, Zhao XQ, Wang J, Wong GK, Yu J: KaKs_Calculator: calculating Ka and Ks through model selection and model averaging. Genomics Proteomics & Bioinformatics 2006, 4(4):259-263.

v • d • e Topics in molecular evolution Natural selection Balancing selection • Directional selection • Disruptive selection • Negative selection • Stabilizing selection • Selective sweep Models Models of DNA evolution • Models of nucleotide substitution • Allele frequency • Ka/Ks ratio • Tajima's D Molecular processes Gene conversion • Gene duplication • Silent mutation • Synonymous substitution

This genetics article is a stub. You can help Wikipedia by expanding it. v • d • e