MKT for coding genes dmel-dsim (5% MAF discarded)

McDonald and Kreitman (1991) proposed a simple test of neutrality (the McDonald-Kreitman test, or MK test), which has become the basis of several methods to estimate the proportion of substitutions that have been fixed by positive selection rather than by genetic drift (Fay et al. 2001; Smith and Eyre-Walker 2002; Sawyer et al. 2003; Bierne and Eyre-Walker 2004; Welch 2006). The test compares the amount of variation within species to the divergence between species at two types of site: synonymous and nonsynonymous sites. The test assumes that all synonymous mutations are neutral, and that nonsynonymous mutations are either strongly deleterious, neutral, or strongly advantageous.

It is expected that the effects on fitness of a mutation are the same whether within a species or at any time along the ancestral history of two species back to the common ancestor. If this is true, and if all mutations are neutral, then the ratio of synonymous to nonsynonymous polymorphisms (Pn/Ps) is expected to equal the ratio of synonymous to nonsynonymous substitutions (Dn/Ds). This is the basis of the MK test. We can summarize the four values as a ratio of ratios termed the Neutrality Index (NI) (Rand and Kann 1996) as follows:

NI = (Pn/Ps) / (Dn/Ds)

Under neutrality, Dn/Ds equals Pn/Ps, and thus NI = 1. If NI < 1, there is an excess of fixation of amino acid replacements due to positive selection (Dn is higher than expected). If NI > 1, negative selection is preventing the fixation of harmful mutations (Dn is lower than expected). The test is therefore useful in assessing the relative importance of neutral drift and selection.