Influence of mutation rate on estimators of genetic differentiation - lessons from Arabidopsis thaliana

If mutation rate is high and migration rate low, classical measures of genetic differentiation are misleading. Only ΦST, an estimator that takes the mutational distances between alleles into account, is independent of mutation rate, for all migration rates. However, the performance of ΦST depends on the underlying mutation model and departures from this model cause its performance to degrade. We further show that QST has the same bias. We provide evidence that, in A. thaliana, microsatellite variation correlates with mutation rate. We thereby demonstrate that our results on estimators of genetic differentiation have important implications, even for species that are well established models in population genetics and molecular biology.We find that alternative measures of differentiation like F'ST and D are not suitable for estimating effective migration rate and should not be used in studies of local adaptation. Genetic differentiation should instead be measured using an estimator that takes mutation rate into account, such as ΦST. Furthermore, in systems where migration between populations is low, such as A. thaliana, QST < FST cannot be taken as evidence for homogenising selection as has been traditionally thought.Characterisation of population structure is a pivotal task in population genetics. It is important for inferring the evolutionary history of a species, assisting in conservation studies [1] and measuring dispersal [2-4]. In association mapping and forensic applications, population structure must be corrected for [see [5]]. The characterisation of population structure is also crucial for studies tracking the signature of local adaptation i. e. when natural selection maintains differences in allele frequencies between populations. Indeed, limited migration or population bottlenecks can also cause allele frequencies to diverge. A proper characterisation of population structure is absolutely required to infer the action of local selection on outlier loci with