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

Abstract
Three 1,000-year-old mycobacterial genomes from Peruvian human skeletons reveal that a member of the Mycobacterium tuberculosis complex derived from seals caused human disease before contact in the Americas. Mycobacterium tuberculosis has a long history as a human pathogen, but how and when this unfortunate relationship began is not clear. Although the strains found in the Americas today are closely related to those in Europe, archaeological evidence suggests that the disease was present in the New World before contact with Europeans. Johannes Krause and colleagues sequenced three approximately 1,000-year-old M. tuberculosis genomes from human remains in Peru, proving that the pathogen caused human disease in the pre-contact New World. The ancient DNA is most closely related to that found in strains adapted to seals and sea lions. The authors hypothesize that these sea mammals may have contracted the disease from an African host species and carried it across the oceans where exploitation of marine resources by coastal peoples of South America allowed zoonotic transfer. This strain of tuberculosis may have then adapted to humans before being replaced by European strains introduced post-contact. 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.