Comparisons between QST and FST-how wrong have we been?

The comparison between quantitative genetic divergence (QST) and neutral genetic divergence (FST) among populations has become the standard test for historical signatures of selection on quantitative traits. However, when the mutation rate of neutral markers is relatively high in comparison with gene flow, estimates of FST will decrease, resulting in upwardly biased comparisons of QST vs. FST. Reviewing empirical studies, the difference between QST and FST is positively related to marker heterozygosity. After refuting alternative explanations for this pattern, we conclude that marker mutation rate indeed has had a biasing effect on published QSTFST comparisons. Hence, it is no longer clear that populations have commonly diverged in response to divergent selection. We present and discuss potential solutions to this bias. Comparing QST with recent indices of neutral divergence that statistically correct for marker heterozygosity (Hedricks G'st and Josts D) is not advised, because these indices are not theoretically equivalent to QST. One valid solution is to estimate FST from neutral markers with mutation rates comparable to those of the loci underlying quantitative traits (e.g. SNPs). QST can also be compared to FST (PhiST) of amova, as long as the genetic distance among allelic variants used to estimate FST reflects evolutionary history: in that case, neutral divergence is independent of mutation rate. In contrast to their common usage in comparisons of QST and FST, microsatellites typically have high mutation rates and do not evolve according to a simple evolutionary model, so are best avoided in QSTFST comparisons.