Transient Darwinian selection in Salmonella enterica serovar Paratyphi A during 450 years of global spread of enteric fever

Abstract

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. pathogen evolution | historical reconstruction | phylogeography

Genome-scale rates of evolutionary change in bacteria

“…We collected 35 whole genome nucleotide SNP alignments from previously published studies (Baines et al, 2015;Bart et al, 2014;Bos et al, 2014;Bratcher et al, 2014;Croucher et al, 2011;Davies et al, 2015;Devault et al, 2014;Eldholm et al, 2015;Gaiarsa et al, 2015;Holden et al, 2013;Holt et al, 2008Holt et al, , 2013Holt et al, , 2016Howden et al, 2013;Marvig et al, 2013;Merker et al, 2015;Njamkepo et al, 2016;Schuenemann et al, 2013;Schultz et al, 2016;Stinear et al, 2014;Uhlemann et al, 2014;Wagner et al, 2014;Ward et al, 2014;Zhou et al, 2013Zhou et al, , 2014, and one unpublished data set of Salmonella enterica serovar Kentucky (Table S1). The Salmonella enterica serovar Kentucky data set comprised 88 strains isolated between 1937 and 2012 (Le Hello et al, 2013).…”

Metagenomics of Two Severe Foodborne Outbreaks Provides Diagnostic Signatures and Signs of Coinfection Not Attainable by Traditional Methods

“…Representative reference strains of E. coli and Salmonella clades were chosen based on the phylogenetic analysis by Luo et al (51) and Zhou et al (52), respectively. The sample-specific bins with more than 1,000 protein-coding genes were included; for S. enterica analysis, the isolates from the outbreaks were also included.…”

Measurably evolving pathogens in the genomic era

“…One limitation of phylogenetic methods such as BEAST is that they do not account for recombination, which can disrupt the temporal signal (see main text). A pragmatic solution is to use a software that can detect recombination such as ClonalFrame [54] and apply BEAST only to the data that were not affected by recombination [58,85]. …”