02101nas a2200193 4500000000100000008004100001260001200042100001500054700000900069700001700078700001300095700001300108245007000121856007000191300001600261490000700277520160900284022001401893 2020 d c10/20201 aDuchĂȘne S1 aHo S1 aCarmichael A1 aHolmes E1 aPoinar H00aThe Recovery, Interpretation and Use of Ancient Pathogen Genomes. uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534838/pdf/main.pdf aR1215-R12310 v303 a

The ability to sequence genomes from ancient biological material has provided a rich source of information for evolutionary biology and engaged considerable public interest. Although most studies of ancient genomes have focused on vertebrates, particularly archaic humans, newer technologies allow the capture of microbial pathogens and microbiomes from ancient and historical human and non-human remains. This coming of age has been made possible by techniques that allow the preferential capture and amplification of discrete genomes from a background of predominantly host and environmental DNA. There are now near-complete ancient genome sequences for three pathogens of considerable historical interest - pre-modern bubonic plague (Yersinia pestis), smallpox (Variola virus) and cholera (Vibrio cholerae) - and for three equally important endemic human disease agents - Mycobacterium tuberculosis (tuberculosis), Mycobacterium leprae (leprosy) and Treponema pallidum pallidum (syphilis). Genomic data from these pathogens have extended earlier work by paleopathologists. There have been efforts to sequence the genomes of additional ancient pathogens, with the potential to broaden our understanding of the infectious disease burden common to past populations from the Bronze Age to the early 20 century. In this review we describe the state-of-the-art of this rapidly developing field, highlight the contributions of ancient pathogen genomics to multidisciplinary endeavors and describe some of the limitations in resolving questions about the emergence and long-term evolution of pathogens.

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