Controversy has surrounded the origin of syphilis since the 15th century. Some have speculated that syphilis arose from a pathogen acquired in the New World by Columbus and his men. Alternative hypotheses are that 1) syphilis was always present in Europe but was previously confused with other diseases such as leprosy; and 2) syphilis arrived in Europe during the Renaissance but originated in Africa and not the New World. A review of the geographical span of the treponematoses over time, as revealed in the paleopathological record, has demonstrated that evidence of treponemal disease is abundant in the Pre-Columbian New World and seemingly absent from European and North African sites. However, isolated reports of treponemal disease in these areas before the 1490s have kept the debate alive. In addition, the relationship between Treponema pallidum subsp. pallidum, the bacterium that causes syphilis, and the other T. pallidum subspecies that cause the similar but non-venereal diseases yaws, endemic syphilis, and pinta continues to puzzle biologists. Although the diseases are characterized by strikingly different symptoms, morphological and genetic differences which can be used to distinguish the pathogens have remained elusive. This project seeks to elucidate the evolutionary trajectory of the subspecies using phylogeography.
Samples have been gathered from cases of syphilis, yaws, and endemic syphilis all over the world. They represent the largest collection of non-venereally transmitted T. pallidum DNA available in a lab collection today. Using targeted genetic analysis, variable sites within and between the subspecies will be identified. Phylogenetic analyses will then be performed upon these differences in order to test various hypotheses regarding the origin of syphilis and the relationship of the T. pallidum subspecies to one another.
This project addresses two long-standing problems in the history of disease while simultaneously studying mechanisms of pathogen evolution in response to human-imposed selective pressures. Because information from phylogenetic methods will join copious paleopathological data on T. pallidum infection in past populations, the proposed research provides a unique opportunity to link adaptive events in a pathogen to changes in epidemiology and disease manifestations as well as host social and sexual practices. This type of knowledge will be applicable to other human pathogens, such as HIV.
Evolutionary changes in transmission, resulting in either a novel mode of infection or greater efficiency in an existing mode, have played important roles in past epidemics and are a major public health concern. This study may elucidate the conditions surrounding and mechanisms underlying such changes and could thus help to inform interventions. In addition, the data produced from comparative genetic analysis may help make sense of puzzling paleopathological findings and dispel the mystery surrounding the origin of syphilis by providing novel objective data. Finally, this study will result in the training of a PhD student.
