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Accurate Inference of Subtle Population Structure (and Other Genetic Discontinuities) Using Principal Coordinates

Author:
Reeves, Patrick A., Richards, Christopher M., Borevitz, Justin O.
ISSN:
1932-6203
Subject:
algorithms, biodiversity, cluster analysis, data collection, evolution, genotype, linkage disequilibrium, loci, models, population structure
Abstract:
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. 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). 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.
Agid:
1215905