Interestingly, the only other confirmed pathogenic mutation at this position (m.14674T>C in mt-tRNAGlu [Horvath et al., 2009b; Uusimaa et al., 2011]) was found to have lower tRNA steady-state levels rather than excess unprocessed intermediates.
In P. carbinolicus, but not in Geobacter species, phosphoenolpyruvate may also be rearranged to phosphonopyruvate by a phosphomutase (Pcar_0628) with 63% sequence identity to the characterized enzyme of Mytilus edulis[ 87], possibly to dispose of excess glycolytic intermediates when the ATP-to-ADP ratio is high.
In such cases, that led to an excess of intermediate frequency mutations (see below).
Tajima's D is positive in all populations, indicating an excess of intermediate alleles.
Positive values for these statistics generally indicate an excess of intermediate frequency alleles which is incompatible with a simple neutral model.
With two subsets of comparable sizes as in figures 1C and 4, this balanced pattern is reflected by an excess of intermediate frequency mutations and departure of the tests in the opposite direction, thus mimicking e.g. simple population substructure (stratification) in the total sample.
A similar excess of intermediate frequency variants was observed in non-African populations, which tend to have positive Tajima's D values at the genome-wide level; yet, the Tajima's D value at NAT2 is unusual in the European and Asian samples (though only marginally significant in the latter) when compared to neutral expectations for two different bottleneck models.
Considering a global advantage of being a slow acetylator (and a roughly equivalent effect of all slow-causing mutations on phenotype and fitness), this model assumes that the different slow variants of NAT2 may have simultaneously become targets of directional selection, thereby generating an excess of intermediate-frequency haplotypes.
Consequently, Tajima's D [21], a summary statistic of the frequency spectrum based on the difference between the Theta estimators, was invariably positive in the continental and in the individual population samples, indicating the excess of intermediate frequency alleles as a feature of NAT2 variation.
Genetic variants tend to be over-estimated for a pooled sample that came from distinct subgroups (such as D7 and D10 in this study), resulting in an excess of intermediate frequency variants, and Tajima's D statistic can be elevated toward a positive value [6].
