The world’s oldest evidence of Treponema pallidum, the bacterium that causes syphilis and several chronic skin infections, has been discovered in 5,500-year-old human bones buried in a rock shelter in Colombia. However, genetic evidence suggests that the person was infected with a previously unknown strain of syphilis, further complicating the already complex picture of syphilis evolution.
Researchers have debated the geographic origin and spread of treponemal diseases (syphilis, Bejel, Framboise, and Pinta) for centuries. All of these are caused by bacteria of the genus Treponema. The best-documented syphilis epidemics occurred in Europe in the 15th century, so early theories held that Christopher Columbus brought syphilis to the Americas, or conversely that the indigenous peoples of the Americas transmitted syphilis to Columbus and his crew.
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In a study published in the journal Science on Thursday (January 22), researchers isolated the oldest syphilis tremolo genome yet from the skeleton of a middle-aged hunter-gatherer buried in Colombia 5,500 years ago.
“Our findings postpone the human relevance of T. pallidum by thousands of years,” study lead author Davide Bozzi, a computational biologist at the University of Lausanne in Switzerland, said in a statement.
The ancient genome of Treponema is very difficult to recover and is usually found in skeletons with bone evidence of Treponema lesions, such as worm-eaten-looking holes in the bones, which are often associated with later stages of infection. Surprisingly, the 5,500-year-old skeleton containing evidence of T. pallidum had no obvious skeletal damage, even though other skeletons from the region had obvious skeletal damage.
While examining the genome of the new syphilis tremolo, which they named TE1-3, researchers discovered that it is a distinct lineage from other previously identified syphilis tremolo subspecies. Based on statistical analysis of differences between the genomes, the researchers estimated that TE1-3 diverged from the current lineage about 13,700 years ago. This suggests that treponemes began circulating in the Americas thousands of years earlier than experts previously thought.
However, the new genome does not reveal whether early treponemal lineages like TE1-3 could have been sexually transmitted, as in venereal syphilis.
“While the current genomic evidence and the genomes presented here do not resolve long-standing debates about the origins of the disease syndrome itself, they do indicate that there is a long evolutionary history of treponemal pathogens and that they were already diversifying in the Americas thousands of years earlier than previously known,” study co-author Elizabeth Nelson, a molecular anthropologist at Southern Methodist University in Dallas, said in a statement.
In a related opinion piece published in Science, Mississippi State University anthropologists Molly Zuckerman and Lydia Bailey, who were not involved in the study, wrote that the new findings “point to the origins of syphilis in the Americas, rather than Europe.” Comparing the increasingly ancient treponemal genome with modern genetic data could inform infection control strategies for syphilis, which has resurfaced globally over the past decade, and could also help researchers understand the history of the infectious disease, the researchers wrote.
“Syphilis in the 15th century was the first emerging infectious disease to emerge globally and may have been a precursor to all subsequent infections, from HIV/AIDS to COVID-19,” Zuckerman and Bailey wrote.
Study co-author Lars Feren-Schmitz, a geneticist at the University of California, Santa Cruz, said in a statement that the new findings demonstrate “the unique potential of paleogenomics to contribute to our understanding of the evolution of species and the potential health risks of past and present communities.”
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