By: Zuri Sullivan
Could the ancestors of this adorable seal have been the source of tuberculosis in the Americas? A recent study published in Nature says it’s possible. A team of geneticists from institutions throughout North America, South America, and Europe, used a comparative genomics approach to try to solve the mystery of the origins of modern M. tuberculosis in the New World.
Mycobacterium tuberculosis (M. tb) is a bacterium that causes tuberculosis disease (TB). TB is the second leading cause of infectious mortality in the world, after HIV, resulting in over 1 million deaths per year. In 2014, the global TB epidemic is largely concentrated in the developing world, but it was only about 50 years ago that the United States was battling its own TB epidemic in New York City.
In fact, the history of TB stretches back to the beginning of human history. The exact date of the origin of TB is still an active question in research, but evidence suggests that the M. tb complex (MTBC) emerged up to 70,000 years ago in Africa and has been co-evolving with humans since then. What remains a mystery, however, is how M. tb spread from the Old World (Africa, Europe, and Asia) to the New World (the Americas). Perhaps the most obvious explanation would be that European settlers brought M. tb with them when they colonized the New World. And there’s a strong precedent for this—the devastating effects of the introduction of pathogens to natives of the New World by European colonists have been an important feature of colonial history. In the case of TB, however, this explanation doesn’t hold up—Bos, et al. isolated M. tb genetic material from three ancient Peruvian skeletons that date back to approximately 1,000 years ago, long before European settlers landed in the New World, but more than 10,000 years after the land bridge across the Bering Strait had been inundated.
This finding set up an interesting conundrum: how did M. tb travel from the Old World to the New World a millennium before humans did so? To answer this question, the authors turned to a comparative genomics approach, analyzing the genomes of mycobacteria from various sources and looking at differences between them to try to determine evolutionary relationships between them. Using a next-generation sequencing technique called Illumina, they analyzed the sequences of M. tb DNA isolated from the Peruvian skeletons, as well as 259 other genomes from human and animal strains of mycobacteria. They then identified single nucleotide polymorphisms (SNPs) present in the various mycobacterial isolates. SNPs are single changes in the genetic code that arise randomly. When they confer a survival advantage to the organism they become evolutionarily selected for. The evolutionary history of a set of organisms can thus be inferred by this type of analysis. This allowed researchers to infer how closely related the different isolates were based on which SNPs they had in common.
Their results were surprising—the ancient Peruvian M. tb isolates were more closely related to animal strains of mycobacteria than to other human strains. In particular, they shared many SNPs with Mycobacterium pinnipedii, a strain of mycobacteria that infects seals and sea lions. Based on these findings, they concluded that the presence of M. tb in the New World could have come from a zoonotic (animal to human) transfer of M. pinnipedii from seals to humans living in ancient coastal communities that hunted these animals.
While it’s currently impossible to go back in time and understand how modern diseases arose, genetic approaches to studying pathogen evolution provide important clues about the history of pathogens and their co-evolution with humans. It is well-documented that ancient pathogens, like M. tb and Plasmodium (the causative agent of malaria) have played an important role in the evolution of our own immune systems. Thus, by unraveling the history of these tiny organisms, we may be able to learn more about how we evolved to fight them.