Title: Combining paleopathology and ancient DNA to infer the paleoepidemiology and evolutionary history of the Mycobacterium tuberculosis complex in pre-conquest Mesoamerica

Authors: Kelly E. Blevins^1,2, Elizabeth A. Nelson³, Alexander Herbig⁴, Johannes Krause⁴, Jane E. Buikstra², Josefina Mansilla Lory⁵, Kirsten I. Bos⁴, and Anne C. Stone²

Affiliations:¹Department of Archaeology, Durham University, Durham, UK; ²Center for Bioarchaeological Research, Arizona State University, Tempe, AZ, USA; ³Institut Pasteur, Microbial Paleogenomics Unit, Paris, France; ⁴Department of Archaeogenetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany; ⁵Dirección de Antropología Física, Instituto Nacional de Antropología e Historia, Ciudad de México, México

Abstract: There is substantial bioarchaeological evidence of tuberculosis (TB) infection throughout the Americas prior to European contact. Evidence in the form of Pott’s disease, or a collapsing spine, is found dating from 700 CE in Peru and 900 CE in the Southwest United States. In 2014, three whole Mycobacterium tuberculosis complex (MTBC) genomes were recovered from pre-contact coastal Peru. These strains were most closely related to M. pinnipedii, the contemporary MTBC strain that infects seals and sea lions. This led to the hypothesis that pinnipeds introduced the MTBC into pre-contact human populations. Discovery of this zoonotic event raised questions about other cases of skeletal TB throughout the Americas and whether they resulted from a human-to-human adapted M. pinnipedii form or a different source. Here we explore this phenomenon by focusing on Tenochtitlan-Tlatelolco, the Mexica (Aztec) imperial capital and contiguous island cities within Lake Texcoco in the Basin of Mexico. Despite its numerous densely populated urban centers, there exists little evidence of TB infection from pre-contact Central Mexico. Two skeletal assemblages from the urban marketplace Tlatelolco were examined, and 2.8% of individuals were found to have skeletal changes suggestive of TB infection. Given the low frequency at which skeletal TB cases occur, this prevalence suggests that TB was endemic in this pre-conquest city. Contextualized by these paleopathological data, we present the results of whole MTBC genome in-solution capture and phylogenetic reconstruction from two Tenochtitlan-Tlatelolco samples. The implications of these results are discussed, as well as the utility of combining paleopathological and ancient DNA datasets.

Funding: All samples were exported and processed with permission from the Instituto Nacional de Antropología e Histora (Oficio 401.B(4)19.2016/36/2099). This work was supported by funding from the National Science Foundation (BCS-1063939 and BCS-1515163), the Max Planck Society,European Research Council Starting Grant CoDisEASe, and a Fulbright-García Robles Fellowship.