A quick comment is that MacLean et al. still did not perform the statistical test properly. When they tested whether the observed N/S number (105/ 64) departures from the expected N/S ratio (2.76 to 3.75, according to their updated analysis), they should use a binomial test, rather than the Chi-squared test as presented in their Table 1. Using the binomial test, we get P = 0.0009 under the expected N/S ratio of 2.76, and P = 4.41e-07 under the expected N/S ratio of 3.75.
Alternatively, if MacLean et al. insisted on using the chi-squared test, the most appropriate approach is to compare the number of mutated N and S sites to the number of non-mutated N and S sites, as I showed previously.