Microbial detection array detects plague in ancient human remains

Scientists studying the origins of infectious disease and population health over time normally find that ancient human remains contain highly degraded DNA in which the pathogen represents only a tiny fraction of the total DNA yield.

Ancient pathogen DNA is heavily mixed with other human and environmental DNA. Lengths of these fragments are often as small as 30 to 50 bases compared with regular DNA fragments that are hundreds to thousands of bases long. The amounts of pathogen in the two samples tested with the LLMDA were three ten-thousandths of the total sample for cholera and eight ten-thousandths for Y. pestis.

We found other pathogens in the chlorea and Y. pestis ancient DNA samples,” Jaing said, noting that tetanus was found along with Y. pestis.

The release notes that beyond showing the potential for microarrays to become a useful screening tool for archaeological samples, the team’s findings demonstrate that the LLMDA can identify primary and/or co-infecting bacterial pathogens in ancient samples.

Developed in early 2008, the LLMDA permits the detection of any virus or bacteria that has been sequenced and included among the instrument’s 135,000 probes — on a one-inch wide, three-inch long glass slide — within 24 hours. The LLMDA version run for the cholera and Y. pestis tests could detect about 1,850 viruses and about 1,400 bacteria.

While the Livermore instrument has previously been used to analyze the purity of infant vaccines, human clinical samples and diseased animals, it had not been deployed to study ancient pathogen DNA until this collaboration.

In Jaing’s view, the value of studying ancient human remains for infectious disease is that the research can offer clues as to how past pandemics happened and why they were so deadly.

By looking at differences between modern DNA and ancient DNA, we may be able to better understand the evolution of diseases and that could help us better understand future disease outbreaks.”

She noted that she believes the use of microarrays will speed up the discovery and identification of pathogens from ancient human remains.

The LLMDA could serve as an excellent screening tool to rapidly identify pathogens. Then genomic sequencing could be used to provide detailed genetic comparison.”

Genomic sequencing is the process of determining the precise order of the four different DNA bases — adenine, guanine, cytosine and thymine — within a cell of anything from bacteria to plants to animals.

Two other institutions participated in the research — the College of Physicians of Philadelphia (Mutter Museum) and the University of South Carolina.

This collaboration has gone very well,” Jaing said. “Our groups have complementary skills and expertise. Hendrik’s group is a leader in biological archaeology and in analyzing ancient DNA. The LLNL team has expertise in microarrays, pathogen detection and bioinformatics.”

— Read more in Alison M. Devault et al., “Ancient pathogen DNA in archaeological samples detected with a Microbial Detection Array,” Scientific Reports 4, article number: 4245 (6 March 2014) (doi:10.1038/srep04245)