Syphilis at the crossroad of phylogenetics and paleopathology

Abstract

The origin of syphilis is still controversial. Different research avenues explore its fascinating history. Here we employed a new integrative approach, where paleopathology and molecular analyses are combined. As an exercise to test the validity of this approach we examined different hypotheses on the origin of syphilis and other human diseases caused by treponemes (treponematoses). Initially, we constructed a worldwide map containing all accessible reports on palaeopathological evidences of treponematoses before Columbus's return to Europe. Then, we selected the oldest ones to calibrate the time of the most recent common ancestor of Treponema pallidum subsp. pallidum, T. pallidum subsp. endemicum and T. pallidum subsp. pertenue in phylogenetic analyses with 21 genetic regions of different T. pallidum strains previously reported. Finally, we estimated the treponemes' evolutionary rate to test three scenarios: A) if treponematoses accompanied human evolution since Homo erectus; B) if venereal syphilis arose very recently from less virulent strains caught in the New World about 500 years ago, and C) if it emerged in the Americas between 16,500 and 5,000 years ago. Two of the resulting evolutionary rates were unlikely and do not explain the existent osseous evidence. Thus, treponematoses, as we know them today, did not emerge with H. erectus, nor did venereal syphilis appear only five centuries ago. However, considering 16,500 years before present (yBP) as the time of the first colonization of the Americas, and approximately 5,000 yBP as the oldest probable evidence of venereal syphilis in the world, we could not entirely reject hypothesis C. We confirm that syphilis seems to have emerged in this time span, since the resulting evolutionary rate is compatible with those observed in other bacteria. In contrast, if the claims of precolumbian venereal syphilis outside the Americas are taken into account, the place of origin remains unsolved. Finally, the endeavor of joining paleopathology and phylogenetics proved to be a fruitful and promising approach for the study of infectious diseases.

Figure 1. Tibiae with treponematosis.

Note the anterior thickening on the tibia depicted on the left side. These bones were excavated at the Brazilian shell mound Jabuticabeira II, which dates to approximately 3,000 yBP.

Figure 2. Hypotheses tested.

The calibration points (obtained from the palaeopathological record) were used as node constrains for phylogenetic analyses to test the following hypotheses on the origin of treponematoses: A) T. pallidum emerged before modern humans evolved, using treponemal evidences in Homo erectus 1.6 million yBP. B) T. pallidum subsp. pallidum emerged from less virulent strains in Europe after Columbus' conquest 500 yBP. C) T. pallidum subsp. pallidum emerged in the time range between 16,500 yBP and 5,000 yBP.

Figure 3. Pre-Columbian Treponematoses map.

Temporal and geographic distribution of osseous evidences of different types of treponematoses. For the underlying bibliography, refer to Table S1.

Figure 4. Geographical and temporal distribution of treponematoses.

A) Percentage of Old World (N = 33) and New World (N = 56) cases of treponematoses, excluding those with uncertain diagnosis or date. B) Percentage of the same cases taken together and distributed according to the corresponding time intervals: 6,000–1,000 BC (N = 15), 1,000 BC–AD 1,000 (N = 29) and AD 1,000-Contact (N = 45). These distributions are based on Table 1.