Genomic Analyses of Ancient Mycobacterium tuberculosis complex Strains from the Americas

Tuberculosis (TB) is an age-old disease caused by members of the Mycobacterium tuberculosis complex (MTBC). TB is thought to have originated in Africa and thereafter spread all over the world. However, its origins in the Americas have always been a matter of debate. Ample skeletal evidence for TB is present in the pre-Columbian Americas. Currently, all MTBC strains found in the Americas are of European origin, suggesting that pre-Columbian MTBC strains were completely replaced by European strains. Previous research from our group led to the recovery of MTBC genomes from three ~1000-year old individuals from coastal Peru. These ancient Peruvian MTBC strains were found to be closely related to MTBC strains currently found only in pinnipeds such as seals and sea lions. The present work aims to determine whether these ancient pinniped-derived MTBC strains spread to the non-coastal parts of the Americas by human-to-human transmission or if there was more than one source of introduction of TB to the pre-Columbian Americas. Samples from pre- and post-Columbian era individuals from South and North America were screened for presence of MTBC DNA using quantitative PCR assays and shotgun sequencing. In-solution target enrichment and sequencing of MTBC-specific genes was used to determine the endogenous DNA content, which ranged from 0.01% to 0.1%. Eleven samples were then enriched for the entire MTBC genome using in-solution capture, and sequencing of these samples is currently in progress.