A treponemal genome from an historic plague victim supports a recent emergence of yaws and its presence in 15th century Europe

Abstract

Developments in techniques for identification of pathogen DNA in archaeological samples can expand our resolution of disease detection. Our application of a non-targeted molecular screening tool for the parallel detection of pathogens in historical plague victims from post-medieval Lithuania revealed the presence of more than one active disease in one individual. In addition to Yersinia pestis, we detected and genomically characterized a septic infection of Treponema pallidum pertenue, a subtype of the treponemal disease family recognised as the cause of the tropical disease yaws. Our finding in northern europe of a disease that is currently restricted to equatorial regions is interpreted within an historical framework of intercontinental trade and potential disease movements. Through this we offer an alternative hypothesis for the history and evolution of the treponemal diseases, and posit that yaws be considered an important contributor to the sudden epidemic of late 15 th century europe that is widely ascribed to syphilis. Ancient DNA analyses have the potential to reveal history that is hidden within archaeological samples. Increased sequencing capacity made available by technological innovations has translated into concomitant increases in temporal depth for human genomes 1 as well as those from commensal 2 and invasive 3 microbes. Genome-level analyses of ancient bacteria and viruses have revealed unexpected patterns of pathogen dispersal in the past, and have prompted discussants to revise long standing theories about the evolution of some of our most well-studied diseases such as plague 4 , tuberculosis 5 and smallpox 6 to name but a few. Genomic investigations of ancient microbes have largely been made possible via selective enrichment for DNA of a target organism. By design, this process requires a priori knowledge of a taxon of interest, which is typically acquired through either initial molecular screening 7 , inference from historical context 8 , diagnostic gross pathology 9 , or combinations thereof 5. More recent approaches have explored the analytical resolution of broad multi-species enrichments 10 or fully non-targeted approaches 11,12 for pathogen detection. Though demonstration of these techniques is currently restricted to single microbial organisms, they indeed offer the flexibility to detect co-morbidities on historical timescales, thus giving a glimpse into past disease ecology. Here we present the application of an ancient pathogen detection method to identify co-morbidities in archaeological specimens associated with an historical epidemic. The influence of co-infections as exacerbating the progression of certain diseases is an established phenomenon 13,14 and has been proposed to partially account for plague's unusually high mortality in the past 15,16 , its potential influence on selective mortality 16 , as well as its persistence and subsequent rapid extinction in post-medieval Europe 8. As a first investigation into the existence of co-morbidities in post-medieval plague victims we a...

Global phylogeny of Treponema pallidum lineages reveals recent expansion and spread of contemporary syphilis

“…Historically, syphilis is commonly believed to have caused a large epidemic across Renaissance Europe, having previously been absent or unrecognized 1,2 . Although the origins of syphilis and the accurate dating of the most recent common ancestor of TPA are still the subject of debate [3][4][5][6] , it is suggested that the strains of TPA that persist in human populations today can be traced back to its introduction into Western Europe approximately 500 years ago, and its subsequent dissemination globally 3,4,6 .Following the introduction of effective antibiotics after World War II, syphilis incidence fluctuated 7 without disappearing, until the 1980s and 1990s during the HIV/AIDS crisis when disease incidence declined markedly 8 , linked to community-wide changes in sexual behaviour, shifting of affected populations, AIDS-related mortality and widespread antimicrobial prophylaxis of HIV-infected populations. However, since the beginning of the twenty-first century, there has been a substantial resurgence in syphilis incidence 9-14 .…”

The Recovery, Interpretation and Use of Ancient Pathogen Genomes

“…The causes of differential mortality within populations had previously received little more than rudimentary attention in most histories of pre-modern disease. Ancient DNA provided a new perspective, by showing endemic infectious diseases increased the risk of dying during times of major epidemics such as the Black Death [ 16 , 17 ]. For instance, Salmonella enterica contributed to catastrophic population collapse in Mesoamerica during the 16 th century European conquest, but also was part of the background disease landscape in 13 th century Norway [ 11 , 18 , 19 ].…”

“…Treponema pallidum pallidum and pertenue (causative agents of syphilis and yaws, respectively) sit at the other end of the spectrum because they lack an outer cell membrane altogether. This feature, coupled with the low pathogenic load of Treponema in late stages of infection [ 45 ], largely precluded its identification in ancient remains [ 45 , 46 , 47 ] until the recent application of high-throughput sequencing methods [ 15 , 17 , 48 ].…”

The Human Osteological Collection of Vilnius University

“…Trauma, tuberculosis, treponematosis, metabolic disorders and endocrine disturbances, skeletal dysplasias, tumors, dental diseases and other topics were studied, while numerous publications received international interest (Jankauskas and Gerhards, 2012). Collaboration with foreign colleagues is essential in this field, therefore the osteological collection was successfully included in the international Global History of Health project (Steckel and Rose, 2002), and was examined for research with the Anthropology Department of the University of Central Florida (Holder et al, 2017;Piličiauskas et al, 2017;Whitmore et al, 2017) and the Max Planck Institute (Giffin et al, 2020). This clearly proves that the human osteological collection in Vilnius University can provide significant data related to certain disease development in the past, or reveal some topics that are still not equally covered in some regions or time periods.…”