Population Genetic Considerations Regarding Evidence for Biased Mutation Rates in Arabidopsis thaliana

Abstract

It has recently been proposed that lower mutation rates in gene bodies compared with upstream and downstream sequences in Arabidopsis thaliana are the result of an "adaptive" modification of the rate of beneficial and deleterious mutations in these functional regions. This claim was based both on analyses of mutation accumulation lines and on population genomics data. Here, we show that several questionable assumptions were used in the population genomics analyses. In particular, we demonstrate that the difference between gene bodies and less selectively constrained sequences in the magnitude of Tajima's D can in principle be explained by the presence of sites subject to purifying selection and does not require lower mutation rates in regions experiencing selective constraints.

Keywords: Tajima's D; mutation rates; population genetics; purifying selection.

Fig. 1.

The solid curves display the ratios of the mean D for 100 basepair mixed sequences to the mean D for 100 basepair neutral sequences, as functions of the selection coefficient against deleterious mutations, s (left-hand Y axes). Note that the scale of these axes differs by panel. The dashed curves display the corresponding measure of skew, Δθ_w (right-hand Y axes). The X-axis uses a log₂ scale. The proportion of neutral sites in the mixed sequences is 0.45. (A–C) These panels have mean neutral D values of −0.9, −0.45, and −0.225, respectively. (D) This panel assumes that there is no distortion of the neutral SFS away from its shape at equilibrium under mutation and drift with constant population size; the mean neutral Ds are slightly negative in this case. Results for several neutral π values (π_n) are shown, corresponding to different mutation rates per basepair (u = 7 ×10^–9 for π_n = 0.003), as indicated by the different colored curves. In panel (D), the mutation rate has no effect on Δθ_w, so that only one curve is shown. In each case, the mutation rates are the same for neutral and mixed sequences.

Fig. 2.

The solid curves display the ratios of the mean D for 100 basepair mixed sequences to the mean D for 100 basepair neutral sequences, as functions of the selection coefficient against deleterious mutations, s (left-hand Y axes). Note that the scale of these axes differs by panel, and a log₂ scale is used for the left-hand Y axes in order to display the lower values of mean D more accurately. The dashed curves display the corresponding measure of skew, Δθ_w (right-hand Y axes). The X-axis uses a log₂ scale. (A) The different colored curves correspond to different proportions of neutral sites in the mixed sequences; the neutral π is 0.003, and the neutral mean D is−0.9. The mutation rate (7 × 10⁻⁹) is the same for both neutral and functional sites. In contrast, in panel (B) the mutation rate is 1.4 × 10⁻⁸ for purely neutral sequences and 7 × 10⁻⁹ for mixed sequences, with π = 0.006 for purely neutral sequences. The different colored curves correspond to different mean D values for neutral sequences (the light blue curves correspond to the case of no skew in the neutral SFS).