An international team of researchers have recently reconstructed the ancient genome of Yersinia pestis, the bacterium that caused the mid-14th century epidemic known as the Black Death. Their findings provide valuable insight for epidemiological discussions of emerging strains of Y. pestis and other pathogens.
In a paper published in Nature, the team reported that the genomes of the ancient and contemporary Y. pestis strains were surprisingly similar. Because contemporary human infections are not as deadly or widespread as the Black Death, researchers previously believed that extant strains differ genetically from their medieval counterpart.
To reconstruct the genome of the ancient strain, the teamextracted DNA from the teeth of four Black Death victims that were buried in mass graves in East Smithfield in London. Due to the decomposition of the skeletal remains, obtaining enough quality DNA of the pathogen to reconstruct an entire genome was very difficult.
“There is very little [pathogen DNA] in a skeleton,” said Krause. “I estimate that probably one in a million [DNA] fragments is pathogen DNA.”
To filter out the pathogen DNA fragments from the rest of the victims’ genetic material,Krause and colleagues used DNA microarray capture technique. After incubating the fossil DNA with the microarray, the scientists captured and enriched the ancient Y. pestis DNA, ending up with about two million unique fragments of bacterial DNA that measured on average about 55 base-pairs long.
Next, the team assembled the genome from these fragments. They used the previously sequenced and assembled genome of an extant Y. pestis strain— CO92—as a reference.
“The orientation of the genes along the chromosome is something very difficult to ascertain in the ancient bug,” said co-author Hendrick Poinar of McMaster University in Canada.
Because the team reconstructed the ancient genome using an extant strain, they could not identify genomic regions that may have existed in medieval Y. pestis but been subsequently lost in CO92. But, according to the researchers, the draft genome still provides important information about the pathogen’s evolution.
In the end, the lack of genetic differences between the ancient and extant strains implies that molecular changes are just one of several factors that are responsible for changes in infectious disease severity and spread. Ultimately, the researchers would like to expand their scope to sequence other ancient infectious pathogens.
“We’ve basically opened up a whole field of research because it’s now possible to study ancient microbes on a whole genomic scale, which can be used for all kinds of infectious diseases,” said Krause.
(1) Bos, K.I., V.J. Schuenemann, G.B. Golding, H.A. Burbano, N. Waglechner, B.K. Coombes, J.B. McPhee, S.N. DeWitte, M. Meyer, et al. 2011. A draft genome of Yersinia pestis from victims of the Black Death. Nat. [Published online October 12, 2011]