Limitations to estimating bacterial cross‐species transmission using genetic and genomic markers: inferences from simulation modeling
Cross-species transmission (CST) of bacterial pathogens has major implications for human health, livestock, and wildlife management because it determines whether control actions in one species may have subsequent effects on other potential host species. The study of bacterial transmission has benefitted from methods measuring two types of genetic variation: variable number of tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). However, it is unclear whether these data can distinguish between different epidemiological sce-narios. We used a simulation model with two host species and known transmis-sion rates (within and between species) to evaluate the utility of these markers for inferring CST. We found that CST estimates are biased for a wide range of parameters when based on VNTRs and a most parsimonious reconstructed phy-logeny. However, estimations of CST rates lower than 5% can be achieved with relatively low bias using as low as 250 SNPs. CST estimates are sensitive to several parameters, including the number of mutations accumulated since introduction, stochasticity, the genetic difference of strains introduced, and the sampling effort. Our results suggest that, even with whole-genome sequences, unbiased estimates of CST will be difficult when sampling is limited, mutation rates are low, or for pathogens that were recently introduced. ; We thank Steven Kalinowsky, Pauline Kamath, Gina K. Hi-mes Boor and Aaron Foley for comments on previous versions of this manuscript. We also thank two anonymous reviewers for their helpful comments. This work was sup-ported by the National Science Foundation and National Institutes of Health Ecology of Infectious Disease (grant number DEB-1067129), the United States Geological Survey and WGFD. The views and opinions in this article are those of the authors and should not be construed to represent any views, determinations, or policies of the US Government. Also, any use of trade, product, or firm names is for descriptive purposes only and does not imply ...