Syphilis origin pinpointed?

John Noble Wilford covers a new article on the New World origin of syphilis, researched by Kristin Harper and George Armelagos.

In her investigation, Ms. Harper studied 22 human Treponemal pallidum strains. The DNA in their genes was sequenced in nearly all cases, examined for changes and eventually used in constructing phylogenetic trees incorporating all variations in the strains.
An Old World yaws subspecies was found to occupy the base of the tree, indicating its ancestral position in the treponemal family, she said. The terminal position of the venereal syphilis subspecies on the tree showed it had diverged most recently from the rest of the bacterial family.
Specimens from two Guyana yaws cases were included in the study, after they were collected and processed by Dr. Silverman. Genetic analysis showed that this yaws strain was the closest known relative to venereal syphilis.

The research article is open access in PLoS Neglected Tropical Diseases. It is a pretty standard phylogenetic analysis, somewhat complicated by the high recombination rate in these bacteria, but the results seem very straightforward. The sister-group relationship of syphilis with Guyana yaws is based on four SNPs, three of which are plausibly selected, so we'll likely hear more on this story in the future.

People sometimes wonder why it matters where syphilis came from. Or worse, they suspect that it is just a front -- a way to play "blame the victim" by putting the origin of the scourge in ancient Americans. This is truly an anthropological topic -- the science of origins is confounded with the subsequent cultural interactions of these populations.

But I think that Armelagos, who has been deeply involved in the problem of syphilis origins for a long time, makes the most relevant connection, as quoted by Wilford:

Dr. Armelagos said research into the origins of syphilis would continue, because "understanding its evolution is important not just for biology, but for understanding social and political history."
Noting that the disease was a major killer in Renaissance Europe, he said, "It could be argued that syphilis is one of the important early examples of globalization and disease, and globalization remains an important factor in emerging diseases."

That to me is an important point worth bringing to my classes. Studying the origins of these epidemics gives us insight about the relationships of global cultural interactions and ecological disruption for new emerging diseases. Syphilis did not merely originate and spread. It also fundamentally changed its nature, with increased virulence and sexual transmission. These changes were adaptive in the context of 16th century global contacts and ecological changes. Maybe the most important changes were in sexual ecology, but sheer numbers may also have been an important catalyst for change. Yaws is a long-term infection that can be sustained in small-scale populations of thousands. Syphilis was introduced and rapidly spread through a population of millions.

The research paper raises an unusual point: answering this question for syphilis may become impossible because its pathogen relatives have been declining:

The large-scale comparative genetic studies possible on the pathogens that cause diseases such as malaria and anthrax will never be possible in T. pallidum [syphilis + yaws], because of the disappearance of the non-venereal treponematoses and the strains that cause them [60],[61]. The prevalence of yaws in Guyana, the last country in South America in which yaws has been documented in recent years, has decreased annually, and surveys carried out by our group in 2006 and 2007 in endemic yaws territory demonstrated no active cases of the disease. Analysis of South American strains is necessary in order to assess the relationship between subsp. pallidum and non-venereal treponemal strains. Because it is not clear whether an opportunity to examine such strains will arise again, the results presented in this paper are of special importance in the debate over the origins of treponemal disease.

Two of the samples in the paper come from degraded old sources -- and they turn out to be the key comparisons. If these species are eradicated it will be a triumph for human health, so there is no reason for sadness (and I suspect no volunteers will be stepping forward to preserve them!). But it does raise an interesting prospect: in at least a few cases, maybe the study of pathogen evolution will become as difficult as the study of human evolution.

References:

Harper KN, Ocampo PS, Steiner BM, George RW, Silverman MS, et al. (2008) On the Origin of the Treponematoses: A Phylogenetic Approach. PLoS Negl Trop Dis 2(1): e148. doi:10.1371/journal.pntd.0000148