McDonald–Kreitman test

The McDonald–Kreitman Test looks for ancient selection over long periods, as opposed to the steady accumulation of mutations that confer no selective advantage predicted by the Neutral theory. It was first devised by John McDonald and Martin Kreitman in 1991, based on an investigation of differences in amino acid sequence of the alcohol dehydrogenase gene of Drosophila species.^[1] Nucleotide differences between the coding regions of homologous genes of related species are enumerated and sorted into four categories, as shown below:

	Fixed	Polymorphic
Synonymous	Ds	Ps
Nonsynonymous	Dn	Pn

Sites are classed as polymorphic if they show any variation within species, while they are classed as fixed if they differ between species but not within them. If the ratio of fixed differences to polymorphisms is much higher for nonsynonymous changes (i.e. D_n/P_n >> D_s/P_s), this indicates that genetic changes have been subject to positive selection.

The McDonald-Kreitman test itself consists of the G-test performed on the numbers in the table above, which would indicate whether the two ratios are significantly different.

As an extension of this, the proportion of base substitutions fixed by natural selection, α, can be estimated:

$\alpha = 1 - \frac{D_sP_n}{D_nP_s}$

45% of amino acid differences between Drosophila simulans and D. yakuba are estimated to have been fixed by selection, while 35% of amino acid differences between primates are estimated to be fixed by selection.^[2]

References

1. ^ McDonald, J. H.; Kreitman, M. (1991). "Adaptive protein evolution at the Adh locus in Drosophila". Nature 351 (6328): 652–654. doi:10.1038/351652a0. PMID 1904993.  edit
2. ^ N.H. Barton, D.E.G. Briggs, J.A. Eisen, D.B. Goldstein, N.H. Patel. Evolution. Cold Spring Harbor. Woodbury, NY. 2007. p.535