Category Archives: Italy

Ötzi’s Lyme Disease in Context

One of the ancient DNA finds that continues to intrigue me is the discovery of Borrelia burgdorferi, the agent of Lyme disease, in Ötzi the 5300-year-old ice mummy from the Italian Alps. As far as I know, this is the only finding of B. burgdorferi in ancient remains of any date.  I discussed the initial report of these findings back in the summer of 2012. 

 

The more we learn about Ötzi’s environment and lifestyle, the less mysterious it seems. There are no signs of human habitation or land management in these high Alpine regions. Indicators of deforestation, farming, and pasture maintenance are lacking from lake sediment and pollen studies. Festi, Putzer and Oeggl (2013) found the first signs of human land management in the Ötztal Alps to began about 1000 years after Ötzi’s time. During the Copper Age, subsistence occupation of the valley floor was sufficient for the population of Ötzi’s time. They did minimal farming, and breeding of caprines (sheep, goats, and ibex). Festi, Putzer and Oeggl (2013) note that Ötzi’s mummy is the only piece of evidence for humans that high in the Otztal Alps before the Bronze Age.

Before Ötzi’s time, landscape management in the Mesolithic was to support red deer herds that were “in a state of semi-domestication by means of active hunting” (Rollo et al, 2002). (Native Americans managed deer populations in similar ways by promoting a landscape where deer thrive near their hunting grounds.) The importance of deer to Ötzi is underscored by everything about him from the red deer meat in his stomach to the roe deerskin that made up his quiver and antler in some of his tools (Rollo et al, 2012). Two different species of deer have been confirmed by genetic analysis.  Most of his clothing was made of sheep and goat skins (O’Sullivan et al, 2016).

The agent of Lyme disease, B. burgdorferi, is transmitted primarily by the tick Ixodes ricinus, common on deer, sheep, cattle, humans and dogs as adults and feed on rodents and small mammals as nymphs. Ticks often thrive at the forest edge where there are grasses for them to climb up to catch passing deer. It seems likely that they would also thrive in along upland forest edges as well. Ixodes ricinus is found throughout the Alps.  It is feasible that Lyme disease was a greater problem for humans when we relied on deer as a staple food.

Ötzi’s B. burgdorferi has yet to be confirmed by a second group. Interestingly, a recent study of B. burgdorferi’s phylogeny suggests that it originated in Europe and later spread to ‘post-Columbian’ North America (Margos et al, 2008). Although Lyme disease was only recognized in the 20th century, it is apparently an ancient disease caused by multiple Borrelia species. And Ötzi’s sequence has not been added to any phylogeny I’ve found, odd. Overlooked, or a problematic sequence?


References

Festi, D., Putzer, A., & Oeggl, K. (2013). Mid and late Holocene land-use changes in the Otztal Alps, territory of the Neolithic Iceman “Otzi”. Quaternary International, 353, 1–18. http://doi.org/10.1016/j.quaint.2013.07.052

Margos, G., Gatewood, A. G., Aanensen, D. M., Hanincová, K., Terekhova, D., Vollmer, S. A., et al. (2008). MLST of housekeeping genes captures geographic population structure and suggests a European origin of Borrelia burgdorferi. Proceedings of the National Academy of Sciences, 105(25), 8730–8735. http://doi.org/10.1073/pnas.0800323105

O’Sullivan, N. J., Teasdale, M. D., Mattiangeli, V., Maixner, F., Pinhasi, R., Bradley, D. G., & Zink, A. (2016). A whole mitochondria analysis of the Tyrolean Iceman’s leather provides insights into the animal sources of Copper Age clothing. Scientific Reports, 6, 1–9. http://doi.org/10.1038/srep31279

Rollo, F., Ubaldi, M., Ermini, L., & Marota, I. (2002). Otzi’s last meals: DNA analysis of the intestinal content of the Neolithic glacier mummy from the Alps. Proceedings of the National Academy of Sciences of the United States of America, 99(20), 12594–12599. http://doi.org/10.1073/pnas.192184599

Early use of the term ‘malaria’

Early use of the term ‘malaria’

I was reading Robert Sallares’ Malaria and Rome this evening and I noticed some information on the earliest use of the term ‘malaria’ that I thought would be worth sharing.

As we have all learned, malaria comes from the Italian mal’ aria, meaning ‘bad air’. A few other interesting facts:

  • Marco Cornaro’s books Scitture della laguna  published in Venice in 1440 is the earliest use of the term mal aere.
  • Horace Walpole was the first to introduce the word malaria to English literature in his Letters in 1740 : “There is a horrid thing called malaria, that comes to Rome every summer, and kills one” (p. 9).
  • Guido Baccelli’s La malaria di Roma, published in 1878, is the first application of the term specifically to the disease.

Does anyone know of earlier uses of the term?

Source: Robert Sallares, Malaria and Rome: A History of malaria in ancient Italy. Oxford University Press, 2002.

 

Metagenomics, Lyme Disease, and the Tyrolean Iceman’s Tattoos

When the genetic analysis of the 5,300 year old Tyrolean Iceman, better known as Ötzi, was published in February, most of the attention was naturally focused on his genomic DNA. His genomic DNA produced some interesting results: he had brown eyes, blood type O+, was probably lactose intolerant and from a southern European gene pool. He also had a collection of alleles that associate with atherosclerosis that correlate with calcifications found by CT scan in Ötzi’s arteries.

To round out a complete analysis of the single 100 mg specimen they took from Ötzi’s ileum, the largest bone of the pelvis, they did a metagenomic analysis to identify all of the non-human DNA sequences amplified. Pelvis is not really an ideal bone to take a specimen from given its proximity to the intestinal organisms that play a role in decomposing the body. Surprisingly, bacterial DNA was a very small 0.84% of the identified sequences. They oddly make no reference to the 18% of DNA reads identified as “other eukaryote”.  Of the bacterial species, 72% of the sequences were from the genus Clostridia, who are primarily spore-forming anaerobes found in the soil. The one pathogen of significance discovered was Borrelia burgdorferi, the agent of Lyme disease.

Iceman metagenome (Keller et al, 2012)
Dark field image of Borrelia burgdorferi. Photo Credit: CDC

The break down of the Iceman’s microbial phylum yielded an impressive array of bacterial diversity.  The Firmicutes include the anaerobic Clorstridium species that are found in the soil. The Proteobacteria include the enteric bacteria like Escherichia coli, many of which are facultative anaerobes. Both of these phylum would be included in decomposition of the body and as anaerobes could grow in the corpse. Borrelia burgdorferi, the agent of Lyme disease, belongs to the phylum Spirochaetes. They were able to sequence approximately 60% of the Borrelia burgdorferi genome. To find B. burgdorferi in the pelvis suggests that the infection was in a systemic phase.

There are two pieces of correlating data to support a Borrelia burgdorferi infection. The international team that did this work linked the infection with Ötzi’s atherosclerosis, an association previously shown between Lyme disease and several other systemic infections.

Tattoos on the Iceman cover or align with major joints and muscles. (South Tyrol Museum of Archaeology site)

Yet, a common symptom of systemic Lyme disease is joint and muscle pain. One of the earliest observations of Ötzi’s mummy is that he has a lot of tattoos specifically placed over joints and muscle groups in places where strain would be expected. These tattoos do not appear to be decorative or signs of inclusion in a community. Consensus appears to have formed early on that these tattoos were medicinal, probably for pain relief. Scans of the mummy do suggest some arthritis. With his lifestyle, an approximately 45-year-old man is expected to have some arthritis and pain.  Both atherosclerosis, and evidence of joint pain and some arthritis can be explained by other means, but when taken together with the B. burgdorferi DNA make a compelling case that Lyme disease contributed to his overall state of health.

Reference:

ResearchBlogging.org

Keller, A., Graefen, A., Ball, M., Matzas, M., Boisguerin, V., Maixner, F., Leidinger, P., Backes, C., Khairat, R., Forster, M., Stade, B., Franke, A., Mayer, J., Spangler, J., McLaughlin, S., Shah, M., Lee, C., Harkins, T., Sartori, A., Moreno-Estrada, A., Henn, B., Sikora, M., Semino, O., Chiaroni, J., Rootsi, S., Myres, N., Cabrera, V., Underhill, P., Bustamante, C., Vigl, E., Samadelli, M., Cipollini, G., Haas, J., Katus, H., O’Connor, B., Carlson, M., Meder, B., Blin, N., Meese, E., Pusch, C., & Zink, A. (2012). New insights into the Tyrolean Iceman’s origin and phenotype as inferred by whole-genome sequencing Nature Communications, 3 DOI: 10.1038/ncomms1701

South Tyrol Museum of Archaeology permanently houses and studies the mummy.