title: The Impact of Selection, Gene Conversion, and Biased Sampling on the Assessment of Microbial Demography.
abstract: Recent studies have linked demographic changes and epidemiological patterns in bacterial populations using coalescent-based approaches. We identified 26 studies using skyline plots and found that 21 inferred overall population expansion. This surprising result led us to analyze the impact of natural selection, recombination (gene conversion), and sampling biases on demographic inference using skyline plots and site frequency spectra (SFS). Forward simulations based on biologically relevant parameters from Escherichia coli populations showed that theoretical arguments on the detrimental impact of recombination and especially natural selection on the reconstructed genealogies cannot be ignored in practice. In fact, both processes systematically lead to spurious interpretations of population expansion in skyline plots (and in SFS for selection). Weak purifying selection, and especially positive selection, had important effects on skyline plots, showing patterns akin to those of population expansions. State-of-the-art techniques to remove recombination further amplified these biases. We simulated three common sampling biases in microbiological research: uniform, clustered, and mixed sampling. Alone, or together with recombination and selection, they further mislead demographic inferences producing almost any possible skyline shape or SFS. Interestingly, sampling sub-populations also affected skyline plots and SFS, because the coalescent rates of populations and their sub-populations had different distributions. This study suggests that extreme caution is needed to infer demographic changes solely based on reconstructed genealogies. We suggest that the development of novel sampling strategies and the joint analyzes of diverse population genetic methods are strictly necessary to estimate demographic changes in populations where selection, recombination, and biased sampling are present.
authors.affiliation: Atelier de Bioinformatique, UMR7205 ISYEB, MNHN-UPMC-CNRS-EPHE, Muséum National d'Histoire Naturelle, Paris, France Collège de France, Center for Interdisciplinary Research in Biology (CIRB), CNRS UMR 7241, Paris, France.
authors.forename: Marguerite
authors.initials: M
authors.lastname: Lapierre
authors.affiliation: Sorbonne Universités, UPMC Univ Paris06, IFD, 4 Place Jussieu, Paris Cedex05, France Institut Pasteur, Microbial Evolutionary Genomics, Paris, France CNRS, UMR3525, Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Blin
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology (CIRB), CNRS UMR 7241, Paris, France UPMC Univ Paris 06, Laboratoire de Probabilités et Modèles Aléatoires (LPMA), CNRS UMR 7599, Paris, France.
authors.forename: Amaury
authors.initials: A
authors.lastname: Lambert
authors.affiliation: Atelier de Bioinformatique, UMR7205 ISYEB, MNHN-UPMC-CNRS-EPHE, Muséum National d'Histoire Naturelle, Paris, France Collège de France, Center for Interdisciplinary Research in Biology (CIRB), CNRS UMR 7241, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Achaz
authors.affiliation: Institut Pasteur, Microbial Evolutionary Genomics, Paris, France CNRS, UMR3525, Paris, France erocha@pasteur.fr.
authors.forename: Eduardo P C
authors.initials: EP
authors.lastname: Rocha
mesh_terms: D001419:Bacteria / Q000235:genetics*; D019143:Evolution, Molecular; D005785:Gene Conversion; D014644:Genetic Variation; D005828:Genetics, Population / Q000379:methods; D016680:Genome, Bacterial; D056186:Metagenomics / Q000379:methods; D008957:Models, Genetic; D015983:Selection Bias; D012641:Selection, Genetic
keywords: Escherichia coli; bacteria; gene conversion; natural selection; population genomics; population size