title: Accurate inference of subtle population structure (and other genetic discontinuities) using principal coordinates.
abstract: BACKGROUND
  Accurate inference of genetic discontinuities between populations is an essential component of intraspecific biodiversity and evolution studies, as well as associative genetics. The most widely-used methods to infer population structure are model-based, Bayesian MCMC procedures that minimize Hardy-Weinberg and linkage disequilibrium within subpopulations. These methods are useful, but suffer from large computational requirements and a dependence on modeling assumptions that may not be met in real data sets. Here we describe the development of a new approach, PCO-MC, which couples principal coordinate analysis to a clustering procedure for the inference of population structure from multilocus genotype data.
  
  
  RESULTS
  PCO-MC uses data from all principal coordinate axes simultaneously to calculate a multidimensional "density landscape", from which the number of subpopulations, and the membership within subpopulations, is determined using a valley-seeking algorithm. Using extensive simulations, we show that this approach outperforms a Bayesian MCMC procedure when many loci (e.g. 100) are sampled, but that the Bayesian procedure is marginally superior with few loci (e.g. 10). When presented with sufficient data, PCO-MC accurately delineated subpopulations with population F(st) values as low as 0.03 (G'(st)>0.2), whereas the limit of resolution of the Bayesian approach was F(st) = 0.05 (G'(st)>0.35).
  
  
  CONCLUSIONS
  We draw a distinction between population structure inference for describing biodiversity as opposed to Type I error control in associative genetics. We suggest that discrete assignments, like those produced by PCO-MC, are appropriate for circumscribing units of biodiversity whereas expression of population structure as a continuous variable is more useful for case-control correction in structured association studies.
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, National Center for Genetic Resources Preservation, Fort Collins, Colorado, United States of America.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Reeves
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Richards
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D016000:Cluster Analysis; D003198:Computer Simulation; D005786:Gene Expression Regulation; D051456:Gene Flow; D005787:Gene Frequency; D017343:Genes, Plant; D005828:Genetics, Population; D018745:Genome, Plant; D005838:Genotype; D008957:Models, Genetic; D015233:Models, Statistical; D008962:Models, Theoretical; D015203:Reproducibility of Results