Category Archives: aDNA

Presentations on the Plague from the European Association of Archaeologists, Vilnius, Lithuania, 2016

I just discovered that most of the presentations from the “Plague in Diachronic and Interdisciplinary Perspective” session of the Europan Association of Archaeologists meeting in Vilnius, Lithuania on 2 September 2016 are now on YouTube.  I think I have collected them all here. Enjoy 3 hours of plague talks!

Introduction-Plague in diachronic and Interdisciplinary perspective by Marcel Keller


From Mild to Murderous: How Yersinia pestis Evolved to Cause Pneumonic Plague by Wyndham Lathem (30 min)


Reconstructing ancient pathogens – discovery of Yersinia pestis in Eurasia 5,000 Years Ago by Simon Rasmussen (15 min)


Plague in the eastern Mediterranean region 1200-1000 BC? by Lars Walloe (15 min)


Placing the Plague of Justinian in the Yersinia pestis phylogenetic context by Jennifer Klunk (15 min)


A demographic history of the plague bacillus revealed through ancient Yersinia pestis genomes by Maria Spyrou (15 min)


Analysis of a High-coverage Yersinia pestis Genome from a 6th Century Justinianic Plague Victim by Michal Feldman (15 min)


Early medieval burials of plague victims: examples from Aschheim and Altenerding (Bavaria, Germany) by Doris Gutsmiedl-Schumann (15 min)


Fleas, rats and other stories – The palaeoecology of the Black Death by Eva Panagiotakopulu (15 min)


Plague in Valencia, 546: A Case Study of the Integration of Texts and Archaeology by Henry Gruber (15 min)


Germany and the Black Death: a zooarchaeological approach by M.A. Paxinos


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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

Evolutionary Clues in 17th-Century Smallpox Genome

By Michelle Ziegler

Smallpox is one of those diseases long believed to have an ancient pedigree, the suspected culprit of legendary epidemics. Yet, so far, smallpox hasn’t made a big impression in ancient DNA surveys. If it was truly endemic throughout the Old World before 1492, so much so that it pops up in the New World almost immediately after contact, it’s odd that it has not been more prominent in ancient DNA surveys. Be ready for a smallpox paradigm shift and reexamination of its reputed history.

In December, Ana Duggan, Maria Perdomo, and the McMaster Ancient DNA Centre team announced the first full ancient smallpox genome isolated from a mummified 17th-century child in Vilnius, Lithuania. Radiocarbon dates of the child place him or her in the mid 17th century (est. c. 1654) in the midst of dated smallpox epidemics from all over Europe.

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Fig 1 (Duggan et al, 2016): Left: Distribution of smallpox records in Europe. Right upper: Dominican Church of the Holy Spirit, Vilnius. Lithuania. Right lower: Crypt containing the child’s remains.

Their finding was unexpected. They were not looking for smallpox at all; the child had no observable lesions. They were hoping to find JC polyomavirus, of particular interest to one of the co-authors, and so they first enriched the specimen for this virus (McKenna 2016). After detecting variola virus (VARV), smallpox, instead they then enriched for VARV to confirm the initial signal.

duggan_cbsmallpox_finalMore than just confirming the signal, they were able to reconstruct the entire genome producing the entire sequence at an average depth of 18X. The surprising child had more revelations in his or her viral sequence. The sequence is ancestral to all existing reference strains. This is consistent with short stretches of aDNA amplified from 300-year-old frozen Siberian remains (Biagini et al, 2012). Unfortunately, the sequences from 2012 were not distinctive enough from the new Lithuanian sequence to give phylogicial resolution between them. Oddly, the frozen Siberian remains also lacked smallpox skin lesions with one showing signs of pulmonary hemorrhages.

Its ancestral position in the phylogeny suggests that a severe bottleneck occurred before c. 1654. As Duggan et al (2016) remark, vaccination would cause a very strong bottleneck, but this occurs after 1654 and there is new diversity among the descendent reference specimens producing two major clades. Yet to be determined is the evolutionary effect of extensive variolation practices in the early modern period. In contrast to vaccination, variolation is a form of intentional smallpox transmission that sometimes went horribly wrong.

Evolution continues unabated. The molecular clock is consistent among the 20th-century specimens and the latest aDNA from the Lithuanian child. The two clades of smallpox collected from 20th-century specimens diverged from each other sometime around the mid-17th century after vaccination began. Interestingly, the less virulent Variola minor strain is not predicted to have emerged from Variola major clade P-II until the mid-19th century.

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Evolutionary history of Variola (Duggan et al, 2016)

It’s not entirely surprising that smallpox, a highly transmissive human-only virus, has a relatively recent last common ancestor; other viruses like measles do as well. Measles last common ancestor is probably in the early 20th century (Furuse, Suzuki & Oshitani, 2010). The dominance of the 1918 influenza strain in recent influenza phylogeny is another example; incomplete because influenza swaps genes with influenza viruses that are circulating primarily in birds, but also in swine and earlier in equines (Taubenberger & Morens, 2005). Improved transmission strains are likely to out-compete strains with a lower transmission rate if they achieve a global spread. For some viruses, though not necessarily all, improved transmissibility and virulence go hand in hand. So, in the end, the relatively recent last common ancestor says more about its global transmissibility than anything else.

The antiquity of the virus needs two components to estimate. The molecular clock must be steady, and it is so far (though this could change with more ancient specimens), and a near relative ‘out group’, related strains outside the Variola clade (a branch of the larger genetic tree). One potential problem here is that as transmissibility improves the clock may speed up. The speed of the clock is determined by the reproduction rate. The relatively steady clock back to this 17th-century specimen suggests that the transmission rate was pretty steady — after the evolutionary/transmission leap that swept aside other Variola strains. The inactivation of several orthopoxvirus genes in smallpox that are functional in vaccinia (used in smallpox vaccines), camelpox, and taterapox  (the ‘out groups’ used) may suggest that one or more of these genes had been protective. When the genes were inactivated, smallpox probably became a much more dangerous virus to humans.

Historical epidemiology suggests that there was once more variation in the virulence of smallpox epidemics.  Securely identifying smallpox epidemics in the historical record is much harder than is generally assumed, and it is harder yet to make a claim for a significant demographic impact prior to the Renaissance (Carmichael & Silverman, 1987). This is the problem with theories that smallpox was the cause of the second-century Antonine plague and then failed to cause an epidemic with a major demographic effect for many centuries. I find this very hard to believe. Additionally, the infamous smallpox epidemics in the New World are now also be reevaluated in ways that diminish smallpox’s toll and add in a wide variety of contributing factors to produce a colonization syndemic. This has most recently been summarized in essays collected in Beyond Germs: Native Depopulation in North America (2015).

One other observation from these studies: All ancient smallpox DNA to date has been extracted from mummy tissue, not a tooth or bone. This may point toward one of the limitations of ancient DNA pathogen surveys that currently use primarily teeth. Since neither mummy had visible smallpox lesions, smallpox should be considered a possibility in any mummy.


References

Duggan, A. T., Perdomo, M. F., Piombino-Mascali, D., Marciniak, S., Poinar, D., Emery, M. V., et al. (2016). 17th Century Variola Virus Reveals the Recent History of Smallpox. Current Biology, 1–7. http://doi.org/10.1016/j.cub.2016.10.061

Biagini, P., Thèves, C., Balaresque, P., Géraut, A., Cannet, C., Keyser, C., et al. (2012). Variola virus in a 300-year-old Siberian mummy. The New England Journal of Medicine, 367(21), 2057–2059. http://doi.org/10.1056/NEJMc1208124

McKenna, Maryn (8 Dec 2016) Child Mummy Found with Oldest Known Smallpox Virus. National Geographic. (online)

Carmichael, A. G., & Silverstein, A. M. (1987). Smallpox in Europe before the seventeenth century: virulent killer or benign disease? Journal of the History of Medicine and Allied Sciences, 42(2), 147–168.

Furuse Y, Suzuki A, & Oshitani H (2010). Origin of measles virus: divergence from rinderpest virus between the 11th and 12th centuries. Virology journal, 7 PMID: 20202190

Taubenberger, J. K., & Morens, D. M. (2005). 1918 Influenza: the mother of all pandemics. Emerging Infectious Diseases, 12(1), 15–22. http://doi.org/10.3201/eid1201.050979

Beyond Germs: Native Depopulation in North America. Edited by Catherine Cameron, Paul Kelton, and Alan Swedlund. University of Arizona Press, 2015.