Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis

Abstract

Modern strains of Mycobacterium tuberculosis from the Americas are closely related to those from Europe, supporting the assumption that human tuberculosis was introduced post-contact1. This notion, however, is incompatible with archaeological evidence of pre-contact tuberculosis in the New World2. Comparative genomics of modern isolates suggests that M. tuberculosis attained its worldwide distribution following human dispersals out of Africa during the Pleistocene epoch3, although this has yet to be confirmed with ancient calibration points. Here we present three 1,000-year-old mycobacterial genomes from Peruvian human skeletons, revealing that a member of the M. tuberculosis complex caused human disease before contact. The ancient strains are distinct from known human-adapted forms and are most closely related to those adapted to seals and sea lions. Two independent dating approaches suggest a most recent common ancestor for the M. tuberculosis complex less than 6,000 years ago, which supports a Holocene dispersal of the disease. Our results implicate sea mammals as having played a role in transmitting the disease to humans across the ocean.

How old are bacterial pathogens?

“…Both studies [55,56] calculated a very similar molecular clock rate, approximately 5 Â 10 28 (electronic supplementary material, table S1). If the clock rate is constant over longer time periods, then that calculation predicts a tMRCA of less than 6000 years for the whole MTBC.…”

“…The older of these two sites was near the coast of Peru, where three genomes were reconstructed from Peruvian Indians who died about 1000 years ago [55]. These genomes belonged to the MTBC, but surprisingly they were most closely related to M. pinnipedii, which infects seals (figure 3a).…”

Parallel detection of ancient pathogens via array-based DNA capture

“…Next generation sequencing as applied to ancient DNA has improved our understanding of the evolutionary history of pathogenic bacteria and the phylogeographic distribution of their associated diseases [1][2][3][4][5][6]. Thus far, most genomic analyses have relied on molecular capture techniques designed to target DNA from individual organisms suspected to have left molecular traces in preserved tissues.…”

“…Thus far, most genomic analyses have relied on molecular capture techniques designed to target DNA from individual organisms suspected to have left molecular traces in preserved tissues. Candidate biological specimens have been selected based on either historical documentation [1,4,6], a burial context that links them to a past pandemic [5], or diagnostic pathological changes that occur in bone as a result of prolonged infection [2,3]. Such exclusive evidence that links an individual to a specific disease, however, is rare in the archaeological record.…”

“…DNA capture microarrays have shown phenomenal success for pathogen DNA retrieval from highly complex ancient DNA extracts [1][2][3][4][5]; hence we have adapted this technology to screen for not just one, but multiple pathogens at the same time.…”