Afarensis

PLoS Neglected Tropical Diseases recently published an interesting article called On the Origin of the Treponematoses: A Phylogenetic Approach. The paper used data from 21 genetic regions in 26 geographically separated strains of the Treponema bacterium. Before looking at the results of the PLoS study, however, a little bit of background is in order.

Treponematosis consists of four syndromes: pinta, yaws, endemic syphilis (or bejel), and venereal syphilis. As the name implies, treponematosis is spread by bacteria of the genus Treponema as follows: pinta (T. careteum), yaws (T. pallidum pertenue), endemic syphilis (T. pallidum endemicum) and venereal syphilis (T. pallidum pallidum). A picture of T. pallidum pallidum is below:
All four are morphologically and immunologically similar (to a greater or lesser extent) and some have argued that they may not be different species. This would imply that the differences in the above diseases were due to differing modes of infection caused by cultural and environmental factors. The idea has some merit because pinta, yaws, and endemic syphilis are common in rural areas with poor sanitation and/or areas were less clothing is worn (they are also spread by skin to skin contact). Venereal syphilis, on the other hand, tends to occur in areas with better sanitation/urban areas (not that the two are synonymous) and/or where more clothing is worn. Added to this, pinta does not produce bony lesions, whereas yaws and endemic syphilis produce lesions virtually indistinguishable from venereal syphilis (although the location and severity of the lesions varies between the three).

In yaws we see, primarily, an inflammatory response in the forearm, hand, and lower leg bones. In extreme cases the anterior portion of the tibia hypertrophies giving a bowed appearance:

This has been called "saber-shin." Endemic syphilis involves the same skeletal changes seen in yaws. Additionally, we see gummatous granulomas on the cranium and long bones, and lesions in the nasal region. In venereal syphilis we see extensive cranial lesions, nasal region destruction, inflammation of the lower limbs (including saber shin) and changes in the elbow, hip, and knee joints. In congenital syphilis (venereal syphilis can be transmitted across the placenta to the developing fetus) we see some of the above, along with poor bone formation, defective incisors, called Hutchinson's incisors, and defective molars, called "mulberry molars." In venereal syphilis the most spectacular and distinctive effect occurs on the crania in the form of caries sicca:

Caries sicca begins as a depression in the outer table of the skull. As the disease progresses the diploe - or middle layer - may be involved. Eventually, the bone heals leaving a raised nodule surrounded by depressed areas of bones. Linear striations - called stellate scaring - can be seen coming of the nodules. So, what we see in the above picture represents a number of healed scars.

Evidence of - Pre-Columbian - treponematosis has been found in populations in the United States, Central American, and South America (mainly Peru and Chile). We also see evidence of treponematosis in Australia and the Pacific Islands. In Europe and Asia the evidence is scanty or controversial.

So, how and where did venereal syphilis originate? There are several schools of thought on the subject, Baker and Armelagos (in their influential paper The Origin and Antiquity of Syphilis) list three. The Columbian hypothesis which states that venereal syphilis originated in the new world and was spread to Europe via the expeditions of Columbus. They argue that the widespread syphilis epidemic that occurred around 1500 indicates a virulent pathogen being spread through a population not previously exposed to it (and therefore lacking immunity to it). The Pre-Columbian hypothesis suggests that venereal syphilis was present in Europe prior to the expeditions of Columbus but was not distinguished from leprosy. Time forbids going into any details on this, but, the bony lesions caused by treponematosis bear some resemblance to those caused by leprosy. Consequently, the syphilis "epidemic" epidemic of 1500 was really an artifact of its recent discovery rather than the result of the introduction of a new disease. Proponents of the Pre-Columbian hypothesis explain the origin of syphilis along the following lines. The treponema bacteria was something we acquired from our simian ancestors and evolved with Homo. As long as populations were small the infections were mild and endemic. Geographical isolation allowed speciation in the treponema bacteria. As populations grew larger more virulent strains were selected for and the bacteria was spread through skin to skin contact. Eventually, living standards began to differentially affect the transmission of the bacteria. The widespread use of clothes in Europe, for example, meant that the bacteria could not be easily spread through skin to skin contact. This favored hardier strains that were sexually transmitted. A variant of this idea has a mutation occurring, around 1500, that caused the venereal form to be more virulent. The more virulent form was subsequently spread by European explorers. Baker and Armelagos also mention a third possibility called the unitarian hypothesis that, in my opinion, isn't that much different from the Pre-Columbian hypothesis.

So, what does the new study say about the origin of venereal syphilis? The authors of the paper examined 22 human T. pallidum strains, one T. pallidum strain from a baboon, and and three T. paraluiscuniculi strains from rabbits. The T. pallidum strains included T. pallidum pertenue and T. pallidum endemicum. DNA was extracted and sequenced (I am omitting the details of that) and a phylogenetic tree was constructed. Here are some of the results:

The phylogenetic tree created in this study sheds light on the relative order in which the T. pallidum subspecies emerged. Subsp. pertenue strains gathered from central Africa and the South Pacific occupy basal positions on the tree, indicating that they most closely resemble the ancestral pathogen in humans...

*snip*

Subsp. endemicum strains, gathered from the Middle East and the Balkans, diverged from subsp. pertenue strains at some later date, and subsp. pallidum strains diverged most recently, indicating that they emerged relatively recently in human history...The topology of the tree is consistent with the long-held belief that treponemal disease is very old and has traveled with humans during their migrations, evolving from ancestral subsp. pertenue, in hot, humid regions, into subsp. endemicum as people settled in cooler and dryer areas, and finally into subsp. pallidum ...

Although the authors of the paper site Hudson (a proponent of the Pre-Columbian hypothesis) in these passages, I am reminded more of the pioneering work of Hackett, at any rate they go on to say:

The genetic analysis of the two subsp. pertenue strains gathered in Guyana demonstrates that they are the closest relatives of venereal syphilis-causing strains identified in this study (Fig. 4). These strains are genetically distinct from Old World subsp. pertenue strains, having diverged more recently than Old-World nonvenereal strains. The geographic analysis of strains, paired with the phylogeny, suggests a three-stage model for T. pallidum's dissemination and evolution. First, T. pallidum arose in the Old World, in the form of non-venereal infection, before spreading with humans to the Middle East/Eastern Europe, in the form of endemic syphilis, and then to the Americas, in the form of New World yaws. Second, a T. pallidum strain from the Americas was introduced back into the Old World, probably as a result of the European exploration of the Americas, becoming the progenitor of modern syphilis-causing strains [bold mine - afarensis]. Third, modern subsp. pallidum strains disseminated from Europe to the rest of the world.

Now what could that bolded part mean?