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.However, only two complete Paratyphi A genomes (20, 21) and five draft genomes (16) have been described.Comparisons of the two complete genomes revealed multiple pseudogenes (20, 21), which were interpreted as reflecting adaptation to its human host, but it is not clear whether the formation of pseudogenes reflects continued adaptation, or is possibly only a transient phenomenon because it results in lessened fitness (22) associated with temporary adaptations to fluctuating environments (23).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.serovar Paratyphi A to address the age and microevolutionary history of one of the major causes of enteric fever.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.
The final set of 149 genomes, including the completed genomes of ATCC 9150 (20) and AKU 12601 (21), yielded a 4,073,403-bp core genome after removing repetitive DNA (henceforth core genome).
It is not possible to reconstruct what the disease burden of enteric fever was in the past because of insufficiently discriminatory historical descriptions of clinical syndromes.
Until the mid-19th century, enteric fever was not even reliably distinguished from typhus (10), which is caused by , and the distinction between serovars Typhi and Paratyphi A was first achieved in 1898 (11).
Otherwise, little is known about its historical patterns of spread or its evolutionary history.
Phylogeographic reconstructions of genetically monomorphic pathogens can be achieved by comparative genomics (3, 4, 6, 19).