On the origin of the treponematoses: a phylogenetic approach

Abstract

Background: Since the first recorded epidemic of syphilis in 1495, controversy has surrounded the origins of the bacterium Treponema pallidum subsp. pallidum and its relationship to the pathogens responsible for the other treponemal diseases: yaws, endemic syphilis, and pinta. Some researchers have argued that the syphilis-causing bacterium, or its progenitor, was brought from the New World to Europe by Christopher Columbus and his men, while others maintain that the treponematoses, including syphilis, have a much longer history on the European continent.

Methodology/principal findings: We applied phylogenetics to this problem, using data from 21 genetic regions examined in 26 geographically disparate strains of pathogenic Treponema. Of all the strains examined, the venereal syphilis-causing strains originated most recently and were more closely related to yaws-causing strains from South America than to other non-venereal strains. Old World yaws-causing strains occupied a basal position on the tree, indicating that they arose first in human history, and a simian strain of T. pallidum was found to be indistinguishable from them.

Conclusions/significance: Our results lend support to the Columbian theory of syphilis's origin while suggesting that the non-sexually transmitted subspecies arose earlier in the Old World. This study represents the first attempt to address the problem of the origin of syphilis using molecular genetics, as well as the first source of information regarding the genetic make-up of non-venereal strains from the Western hemisphere.

Figure 1. Genome coordinates of the 21 regions targeted for sequencing.

The name of the genes and/or intergenic regions (IGRs) amplified are shown in bold next to their numeric coordinates and a point denoting their location in the genome. The coordinates of the nucleotides sequenced within each gene/IGR can be found in Table 2.

Figure 2. Comparison of 17 single nucleotide polymorphisms present in pathogenic Treponema strains, including 2 strains of T. pallidum subsp. pertenue gathered from Guyana.

Figure 3. A phylogenetic tree depicting the relationships between the T. pallidum subspecies.

This maximum likelihood tree is based on 20 polymorphic regions in the T. pallidum genome. Bootstrap support was estimated with 1,000 replicates in order to assess confidence at branching points and are shown within circles where values are high (>90%). Bootstrap support values for both maximum likelihood and maximum parsimony trees are shown, in that order.

Figure 4. A network path for four informative substitutions shows that New World subsp. pertenue, or yaws-causing strains, are the closest relatives of modern subsp. pallidum strains.

The geographical distribution of the endemic treponemal diseases circa 1900 is shown, based on a map created by Hackett . Each polymorphism pattern is linked to the sites where the strains that contain it were gathered. Arrows convey the directionality of change, determined from the previously built phylogenetic tree as described in the text. The four substitutions were located in two genes located on separate sides of the genome, tprI and gpd. The locations from which subsp. pallidum strains were gathered are listed in Table 1.