RESUMO
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.
Assuntos
Bactérias/genética , Conversão Gênica , Seleção Genética , Evolução Molecular , Variação Genética , Genética Populacional/métodos , Genoma Bacteriano , Metagenômica/métodos , Modelos Genéticos , Viés de SeleçãoRESUMO
Multidrug resistant and hypervirulent clones of Klebsiella pneumoniae are emerging pathogens. To understand the association between genotypic and phenotypic diversity in this process, we combined genomic, phylogenomic and phenotypic analysis of a diverse set of K. pneumoniae and closely related species. These species were able to use an unusually large panel of metabolic substrates for growth, many of which were shared between all strains. We analysed the substrates used by only a fraction of the strains, identified some of their genetic basis, and found that many could not be explained by the phylogeny of the strains. Puzzlingly, few traits were associated with the ecological origin of the strains. One noticeable exception was the ability to use D-arabinose, which was much more frequent in hypervirulent strains. The broad carbon and nitrogen core metabolism of K. pneumoniae might contribute to its ability to thrive in diverse environments. Accordingly, even the hypervirulent and multidrug resistant clones have the metabolic signature of ubiquitous bacteria. The apparent few metabolic differences between hypervirulent, multi-resistant and environmental strains may favour the emergence of dual-risk strains that combine resistance and hypervirulence.
Assuntos
Arabinose/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Genoma Bacteriano/genética , Klebsiella pneumoniae/crescimento & desenvolvimento , Klebsiella pneumoniae/genética , Sequência de Bases , Carbono/metabolismo , DNA Bacteriano/genética , Genômica , Genótipo , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/patogenicidade , Nitrogênio/metabolismo , Fenótipo , Filogenia , Análise de Sequência de DNARESUMO
Multiple epidemic diseases have been designated as emerging or reemerging because the numbers of clinical cases have increased. Emerging diseases are often suspected to be driven by increased virulence or fitness, possibly associated with the gain of novel genes or mutations. However, the time period over which humans have been afflicted by such diseases is only known for very few bacterial pathogens, and the evidence for recently increased virulence or fitness is scanty. Has Darwinian (diversifying) selection at the genomic level recently driven microevolution within bacterial pathogens of humans? Salmonella enterica serovar Paratyphi A is a major cause of enteric fever, with a microbiological history dating to 1898. We identified seven modern lineages among 149 genomes on the basis of 4,584 SNPs in the core genome and estimated that Paratyphi A originated 450 y ago. During that time period, the effective population size has undergone expansion, reduction, and recent expansion. Mutations, some of which inactivate genes, have occurred continuously over the history of Paratyphi A, as has the gain or loss of accessory genes. We also identified 273 mutations that were under Darwinian selection. However, most genetic changes are transient, continuously being removed by purifying selection, and the genome of Paratyphi A has not changed dramatically over centuries. We conclude that Darwinian selection is not responsible for increased frequency of enteric fever and suggest that environmental changes may be more important for the frequency of disease.
Assuntos
Saúde Global , Salmonella enterica/genética , Seleção Genética , Febre Tifoide/epidemiologia , Genes Bacterianos , Humanos , Polimorfismo de Nucleotídeo Único , Febre Tifoide/microbiologiaRESUMO
The first Lactobacillus delbrueckii ssp. bulgaricus genome sequence revealed the presence of a very large inverted repeat (IR), a DNA sequence arrangement which thus far seemed inconceivable in a non-manipulated circular bacterial chromosome, at the replication terminus. This intriguing observation prompted us to investigate if similar IRs could be found in other bacteria. IRs with sizes varying from 38 to 76 kbp were found at the replication terminus of all 5 L. delbrueckii ssp. bulgaricus chromosomes analysed, but in none of 1373 other chromosomes. They represent the first naturally occurring very large IRs detected in circular bacterial genomes. A comparison of the L. bulgaricus replication terminus regions and the corresponding regions without IR in 5 L. delbrueckii ssp. lactis genomes leads us to propose a model for the formation and evolution of the IRs. The DNA sequence data are consistent with a novel model of chromosome rescue after premature replication termination or irreversible chromosome damage near the replication terminus, involving mechanisms analogous to those proposed in the formation of very large IRs in human cancer cells. We postulate that the L. delbrueckii ssp. bulgaricus-specific IRs in different strains derive from a single ancestral IR of at least 93 kbp.
Assuntos
Cromossomos Bacterianos/química , DNA Bacteriano/genética , Evolução Molecular , Genoma Bacteriano , Sequências Repetidas Invertidas , Lactobacillus delbrueckii/genética , Replicação do DNA , DNA Circular/genética , Lactobacillus delbrueckii/classificação , Modelos Genéticos , Filogenia , Análise de Sequência de DNARESUMO
Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.