NEW YORK – An international team led by investigators in Germany and the US has sequenced a handful of ancient Salmonella genomes, uncovering a cluster of relatively unspecialized bugs in the same lineage that produced the human-specific pathogen S. enterica Paratyphi C.
The researchers, who reported their findings Monday in Nature Ecology and Evolution, also saw a shift toward host-specific S. enterica strains in cultures with more agricultural lifestyles.
"Bacterial genomic comparisons suggest that the earlier ancient strains were not host-specific, differed in pathogenic potential, and experienced convergent pseudogenization that accompanied their downstream host adaptation," wrote co-senior and corresponding authors Johannes Krause and Alexander Herbig, archaeogenetics researchers at the Max Planck Institute for the Science of Human History, further noting that "the emergence of human-adapted S. enterica is linked to human cultural transformations."
The team focused on the Neolithic period, reasoning that the closer contact with domestic animals during the transition from foraging lifestyles to cultures that relied more heavily on agriculture and pastoralism may have led to a rise in bacterial pathogens that swapped back and forth between humans and animals.
"[D]irect molecular evidence — such as ancient DNA — in support of this hypothesis is currently missing," the authors wrote. "Microbial paleogeneomics provides a unique window into the past human infectious disease burden, and promises to elucidate the deep evolutionary history of clinical relevant pathogens."
After screening through more than 2,700 metagenome sequences from ancient human skeletons, Krause, Herbig, and colleagues focused in on eight Salmonella enterica sub-species enterica isolates from individuals in forager, pastoral, and agropastoral groups. From there, they relied on in-solution capture to grab S. enterica isolates from ancient skeletal samples dated at some 1,500 to 6,500 years old from sites in Russia, Switzerland, Turkey, and Italy, ultimately sequencing the genomes of eight S. enterica isolates.
"[T]he eight bacterial genomes transect 4,700 years of S. enterica infections during the spread of an [agro-]pastoralist subsistence," the authors noted, "and can provide an unprecedented view into the diversity and evolution of S. enterica during this transformative time."
When the team analyzed whole-genome sequences from the ancient bugs alongside available sequences for 2,961 modern S. enterica isolates, it identified a cluster dubbed the "Ancient Eurasian Super Branch" (AESB) that contained early forms of S. enterica without host specificity.
"Despite the high genetic diversity of S. enterica, all ancient bacterial genomes clustered in a single previously uncharacterized branch that contains S. enterica adapted to multiple mammalian species," the authors reported. "All ancient bacterial genomes from prehistoric (agro-)pastoralists fall within a part of this branch that also includes the human-specific S. enterica Paratyphi C, illustrating the evolution of a human pathogen over a period of 5,000 years."
By bringing in available sequence data for hundreds more present-day members of the AESB lineage, meanwhile, the researchers phylogenetically retraced the advent of host-specific and pathogenic lineages falling within the broader cluster within the context of human lifestyle transitions. In particular, they highlighted more than two-dozen genes that have undergone multiple pseudogenization events through convergent evolution in lineages with host specialization.
"The AESB harbors six different host-adapted S. enterica serovars, several serovars that are host-unrestricted, and the predict host-unrestricted strains older than 3,000 years," the authors reported, noting that "all modern host-adapted serovars carry largely distinct sets of pseudogenes irrespective of relatedness, which is in line with previous results in S. enterica and suggests a primary independent evolution of pseudogenes. However, shared pseudogenes that are formed independently probably represent key changes necessary for host adaptation."