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      An African origin for Mycobacterium bovis

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          Abstract

          Background and objectives

          Mycobacterium bovis and Mycobacterium caprae are two of the most important agents of tuberculosis in livestock and the most important causes of zoonotic tuberculosis in humans. However, little is known about the global population structure, phylogeography and evolutionary history of these pathogens.

          Methodology

          We compiled a global collection of 3364 whole-genome sequences from M.bovis and M.caprae originating from 35 countries and inferred their phylogenetic relationships, geographic origins and age.

          Results

          Our results resolved the phylogenetic relationship among the four previously defined clonal complexes of M.bovis, and another eight newly described here. Our phylogeographic analysis showed that M.bovis likely originated in East Africa. While some groups remained restricted to East and West Africa, others have subsequently dispersed to different parts of the world.

          Conclusions and implications

          Our results allow a better understanding of the global population structure of M.bovis and its evolutionary history. This knowledge can be used to define better molecular markers for epidemiological investigations of M.bovis in settings where whole-genome sequencing cannot easily be implemented.

          Lay summary

          During the last few years, analyses of large globally representative collections of whole-genome sequences (WGS) from the human-adapted Mycobacterium tuberculosis complex (MTBC) lineages have enhanced our understanding of the global population structure, phylogeography and evolutionary history of these pathogens. In contrast, little corresponding data exists for M. bovis, the most important agent of tuberculosis in livestock. Using whole-genome sequences of globally distributed M. bovis isolates, we inferred the genetic relationships among different M. bovis genotypes distributed around the world. The most likely origin of M. bovis is East Africa according to our inferences. While some M. bovis groups remained restricted to East and West Africa, others have subsequently dispersed to different parts of the world driven by cattle movements.

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          Most cited references37

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          A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data.

          Heng Li (2011)
          Most existing methods for DNA sequence analysis rely on accurate sequences or genotypes. However, in applications of the next-generation sequencing (NGS), accurate genotypes may not be easily obtained (e.g. multi-sample low-coverage sequencing or somatic mutation discovery). These applications press for the development of new methods for analyzing sequence data with uncertainty. We present a statistical framework for calling SNPs, discovering somatic mutations, inferring population genetical parameters and performing association tests directly based on sequencing data without explicit genotyping or linkage-based imputation. On real data, we demonstrate that our method achieves comparable accuracy to alternative methods for estimating site allele count, for inferring allele frequency spectrum and for association mapping. We also highlight the necessity of using symmetric datasets for finding somatic mutations and confirm that for discovering rare events, mismapping is frequently the leading source of errors. http://samtools.sourceforge.net. hengli@broadinstitute.org.
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            Time dependency of molecular rate estimates and systematic overestimation of recent divergence times.

            Studies of molecular evolutionary rates have yielded a wide range of rate estimates for various genes and taxa. Recent studies based on population-level and pedigree data have produced remarkably high estimates of mutation rate, which strongly contrast with substitution rates inferred in phylogenetic (species-level) studies. Using Bayesian analysis with a relaxed-clock model, we estimated rates for three groups of mitochondrial data: avian protein-coding genes, primate protein-coding genes, and primate d-loop sequences. In all three cases, we found a measurable transition between the high, short-term (< 1-2 Myr) mutation rate and the low, long-term substitution rate. The relationship between the age of the calibration and the rate of change can be described by a vertically translated exponential decay curve, which may be used for correcting molecular date estimates. The phylogenetic substitution rates in mitochondria are approximately 0.5% per million years for avian protein-coding sequences and 1.5% per million years for primate protein-coding and d-loop sequences. Further analyses showed that purifying selection offers the most convincing explanation for the observed relationship between the estimated rate and the depth of the calibration. We rule out the possibility that it is a spurious result arising from sequence errors, and find it unlikely that the apparent decline in rates over time is caused by mutational saturation. Using a rate curve estimated from the d-loop data, several dates for last common ancestors were calculated: modern humans and Neandertals (354 ka; 222-705 ka), Neandertals (108 ka; 70-156 ka), and modern humans (76 ka; 47-110 ka). If the rate curve for a particular taxonomic group can be accurately estimated, it can be a useful tool for correcting divergence date estimates by taking the rate decay into account. Our results show that it is invalid to extrapolate molecular rates of change across different evolutionary timescales, which has important consequences for studies of populations, domestication, conservation genetics, and human evolution.
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              SIMMAP: Stochastic character mapping of discrete traits on phylogenies

              Background Character mapping on phylogenies has played an important, if not critical role, in our understanding of molecular, morphological, and behavioral evolution. Until very recently we have relied on parsimony to infer character changes. Parsimony has a number of serious limitations that are drawbacks to our understanding. Recent statistical methods have been developed that free us from these limitations enabling us to overcome the problems of parsimony by accommodating uncertainty in evolutionary time, ancestral states, and the phylogeny. Results SIMMAP has been developed to implement stochastic character mapping that is useful to both molecular evolutionists, systematists, and bioinformaticians. Researchers can address questions about positive selection, patterns of amino acid substitution, character association, and patterns of morphological evolution. Conclusion Stochastic character mapping, as implemented in the SIMMAP software, enables users to address questions that require mapping characters onto phylogenies using a probabilistic approach that does not rely on parsimony. Analyses can be performed using a fully Bayesian approach that is not reliant on considering a single topology, set of substitution model parameters, or reconstruction of ancestral states. Uncertainty in these quantities is accommodated by using MCMC samples from their respective posterior distributions.
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                Author and article information

                Journal
                Evol Med Public Health
                Evol Med Public Health
                emph
                Evolution, Medicine, and Public Health
                Oxford University Press
                2050-6201
                2020
                31 January 2020
                31 January 2020
                : 2020
                : 1
                : 49-59
                Affiliations
                [e1 ] Molecular Parasitology and Infection Biology, Swiss Tropical and Public Health Institute , Basel, Switzerland
                [e2 ] University of Basel , Basel, Switzerland
                [e3 ] Mycobacterial Diseases Directorate, Armauer Hansen Research Centre , Addis Ababa, Ethiopia
                [e4 ] Department of Animal Science and Range Management, Bule Hora University , Bule Hora Town, Ethiopia
                [e5 ] Aklilu Lemma Institute of Pathobiology, Addis Ababa University , Addis Ababa, Ethiopia
                [e6 ] Bacteriology Department, Animal & Plant Health Agency (APHA) , Weybridge, Surrey, UK
                [e7 ] Mycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine , Antwerp, Belgium
                [e8 ] Collection of Mycobacterial Cultures (BCCM/ITM), Institute of Tropical Medicine , Antwerp, Belgium
                [e9 ] Department of Biomedical Sciences, Antwerp University , Antwerp, Belgium
                [e10 ] Diagnostic Bacteriology and Pathology Laboratory, National Veterinary Services Laboratories, United States Department of Agriculture , Ames, IA, USA
                Author notes
                Corresponding authors. Sebastien Gagneux: Tel: +41 61 284 8369; Fax: +41 61 284 8101; E-mail: sebastien.gagneux@ 123456swisstph.ch ; Daniela Brites: Tel: +41 61 284 8185; Fax: +41 61 284 8101; d.brites@ 123456swisstph.ch

                Chloé Loiseau and Fabrizio Menardo contributed equally to this work.

                Author information
                http://orcid.org/0000-0002-8090-2287
                Article
                eoaa005
                10.1093/emph/eoaa005
                7081938
                32211193
                84085f80-a513-4074-9f59-15f8c98bfba7
                © The Author(s) 2020. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 August 2019
                : 24 December 2019
                : 24 January 2020
                Page count
                Pages: 11
                Funding
                Funded by: Swiss National Science Foundation, DOI 10.13039/501100001711;
                Award ID: 310030_166687
                Award ID: 310030_188888
                Award ID: IZRJZ3_164171
                Award ID: IZLSZ3_170834
                Award ID: CRSII5_177163
                Funded by: European Research Council, DOI 10.13039/100010663;
                Award ID: 309540-EVODRTB
                Funded by: SystemsX.ch, DOI 10.13039/501100012390;
                Categories
                Original Research Article

                mycobacterium bovis,zoonosis,bovine tuberculosis,whole-genome sequencing,phylogeography,molecular clock

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