Wednesday, October 28, 2015

Striking Gold (Teeth) with Ancient Plague DNA

Fig.1. Scanning electron micrograph of Yersinia pestis bacteria mass in foregut of a flea
(Credit: Rocky Mountain Laboratories, NIAID, 2010)

Since the beginning of the year, fifteen people in the United States have been infected with the bubonic plague, and four of those individuals have died. This disease, often only mentioned in context of the Black Death (1346-1353 AD) or the Justinian Plague (541-542 AD), still exists today in pockets around the world. The causative pathogen Yersinia pestis hides in natural reservoirs, such as black-tailed prairie dogs in the southwestern United States or marmots in the Eurasian Steppe, only to flare up in human populations when rodents and the fleas they carry get too close.

Despite the deadly history of the disease - the Black Death killed an estimated 60 percent of the European population - Y. pestis evolved from a much less virulent ancestor that caused symptoms closer to the common cold. Previous research pinpointed the first appearance of this bacterium in skeletal remains at 1,500 years ago, but a study released last week in the journal Cell pushes that date back to more than 5,000 years ago.

Fig.2. Engraving of a plague doctor in 17th century Rome
(Credit: Paul F├╝rst, 1656)

Plague in Ancient Teeth

Co-author Simon Rasmussen from the Technical University of Denmark worked with an international team of researchers to sequence and map ancient strains of Y. pestis. The group examined teeth from 101 museum and excavation specimens from Europe and Central Asia that dated 2,800 to 5,000 years ago. DNA analyses of drillings from the teeth revealed that seven of those individuals were infected with plague bacteria.

The sequences of ancient Y. pestis were studied for specific genes known to contribute to the virulence of the pathogen. Six of the seven samples were missing two important genes found in strains associated with the Justinian Plague and the Black Death. The ymt gene allows the bacteria to survive and multiply in the flea’s gut, which effectively starves the flea and forces it to feed on more hosts, therefore spreading the disease. These sequences also lacked the pla gene, which enables the spread of Y. pestis from the lungs into other tissues, turning a lung infection into something much more dangerous.

The seventh sample came from Armenia in 951 BC and contained both ymt and pla, that contribute to rapid spread of a deadlier form of the disease by fleas. Due to the origin and the younger age of the sample, the researchers hypothesize the deadly mutations developed either in Eurasia during the first millennium BC or earlier in the Middle East.

Fig.3. This Oropsylla Montana adult male can act as a plague vector in the United States.
(Credit: Kat Masback via Flickr, 2009

Setting the Molecular Clock

Rasmussen et al. relied on the molecular clock of Yersinia pestis, which allowed them to create an evolutionary history based on the known rate of mutation in the species and push the recorded appearance of the plague back 2,000 years. They propose that although the ancient plague pathogen was not nearly as deadly as later strains, population declines in the late 4th and early 3rd millennia BC could be due to the disease. High rates of human migration during that time would have spread the plague to new areas in Eurasia.

Although Rasmussen et al. created a longer timeline for the disease, research released last month in the Journal of Medical Entomology examined a 20-million-year-old flea trapped in amber with possible Yersinia bacteria attached to its proboscis. If the bacteria truly is a relative of the plague pathogen, the relation between Yersinia and fleas could stretch back even further. Unfortunately, the amber prevents a more thorough examination of morphological characteristics or genetic sequences.

Both studies, however, show the ongoing fascination people have with the disease that contributed to the deaths of millions throughout history as well as the possible collapse of civilizations. The teeth recovered from excavations and museums provide hard evidence for the evolution of one of the most deadly pathogens. Furthermore, they allowed researchers to trace the origin of a disease and understand how infection shaped human history.


References:
Ho, S. (2008). The Molecular Clock and Estimating Species Divergence. Nature Education, vol. 1 (1): 168. Retrieved from http://www.nature.com/scitable/topicpage/the-molecular-clock-and-estimating-species-divergence-41971

Poinar, G. A New Genus of Fleas with Associated Microorganism in Dominican Amber. Journal of Medical Entomology, tjv 134. doi:10.1093/jme/tjv134

Rasmussen, et al. (2015, October 22). Early Divergent Strains of Yersinia pestis in Eurasia 5,000 Years Ago. Cell, vol. 163 (3): 571-582. doi:10.1016/j.cell.2015.10.009



Glossary

bubonic plague
One of three types of plague caused by the Yersinia pestis bacterium that causes enlarged and painful lymph nodes.
virulence
A measure of the pathogen’s likelihood to cause disease or the severity of that disease.
molecular clock
The evolutionary history of species based on their rate of molecular change over time and environmental constraints.
proboscis
Elongated, usually tubular, mouthpart in insects.

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