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. 2025 Apr;640(8057):186-193.
doi: 10.1038/s41586-024-08515-5. Epub 2024 Dec 18.

Ancient genomes reveal a deep history of Treponema pallidum in the Americas

Rodrigo Barquera #  1 , T Lesley Sitter #  1 , Casey L Kirkpatrick #  1   2   3 , Darío A Ramirez #  4   5 , Arthur Kocher  1 , Maria A Spyrou  1   6 , Lourdes R Couoh  7 , Jorge A Talavera-González  7 , Mario Castro  8   9 , Tanya von Hunnius  10 , Evelyn K Guevara  11 , W Derek Hamilton  12 , Patrick Roberts  13 , Erin Scott  14 , Mariana Fabra  4   5 , Gabriela V Da Peña  15   16 , Aryel Pacheco  17 , Mónica Rodriguez  18 , Eugenio Aspillaga  19 , Anthi Tiliakou  1 , Elizabeth A Nelson  1   20 , Karen L Giffin  1 , Raffaela A Bianco  1 , Adam B Rohrlach  1   21   22 , María de Los Ángeles García Martínez  23 , Fabiola A Ballesteros Solís  7 , Antti Sajantila  11   24 , Shelley R Saunders  10 , Rodrigo Nores  4   5 , Alexander Herbig  1 , Johannes Krause  25 , Kirsten I Bos  26
Affiliations

Ancient genomes reveal a deep history of Treponema pallidum in the Americas

Rodrigo Barquera et al. Nature. 2025 Apr.

Abstract

Human treponemal infections are caused by a family of closely related Treponema pallidum that give rise to the diseases yaws, bejel, pinta and, most notably, syphilis1. Debates on a common origin for these pathogens and the history of syphilis itself have weighed evidence for the 'Columbian hypothesis'2, which argues for an American origin, against that for the 'pre-Columbian hypothesis'3, which argues for the presence of the disease in Eurasia in the Medieval period and possibly earlier. Although molecular data has provided a genetic basis for distinction of the typed subspecies4, deep evolution of the complex has remained unresolved owing to limitations in the conclusions that can be drawn from the sparse palaeogenomic data that are currently available. Here we explore this evolutionary history through analyses of five pre- and peri-contact ancient treponemal genomes from the Americas that represent ancient relatives of the T. pallidum subsp. pallidum (syphilis), T. pallidum subsp. pertenue (yaws) and T. pallidum subsp. endemicum (bejel) lineages. Our data indicate unexplored diversity and an emergence of T. pallidum that post-dates human occupation in the Americas. Together, these results support an American origin for all T. pallidum characterized at the genomic level, both modern and ancient.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Contextual details of the five individuals who yielded treponemal genomes in this study.
a, Map showing locations of the archaeological sites where the individuals were found. b, Image of skeleton MXV001 in situ in northern Mexico City. c, Femur from Mexico City that yielded genome RAZ007. d, Immature molar (JUC013.A) with unfused roots that yielded genome JUC013. e, Image of the mature tibia (GAP009.A) that yielded genome GAP009. f, Upper left second molar (DFU001.A) that yielded genome DFU001. g, Calibrated 14C radiocarbon data for all individuals. OxCal v4.4.4; r:5 (Bronk Ramsey); atmospheric data from Hogg et al. and Reimer et al.; marine data from Heaton et al.. For the calibrated date interval, the upper brackets designate 1σ ranges (68.3% probability) and the lower brackets designate 2σ ranges (95.4% probability).
Fig. 2
Fig. 2. Circos plot showing genome features of the TPA Nichols reference genome and additional tracks containing metadata specific to the five ancient genomes presented here.
Gridlines on the average distributions for DFU001, JUC013 and RAZ007 (twofold read support) and GAP009 and MXV001 (fivefold read support). Numbers along the outer circumference indicate coordinates in kb. rRNA, ribosomal RNA.
Fig. 3
Fig. 3. Maximum likelihood-based phylogenetic reconstruction.
The reconstruction is based on 2,104 SNPs called at fourfold allele support with recombinant and low-confidence regions removed, and 1,000 bootstrap replicates with 25% permission for missing data. Branches with bootstrap support of at least 70% are represented with a dot and the support value. Names of ancient genomes are coloured according to their corresponding clade. Placements of the lower coverage genomes CHS119, SJ219, 133 and RAZ007 are shown with dotted lines and were made on the basis of their position in trees generated with twofold allele support (Supplementary Fig. 17). Asterisks indicate data generated in this study. ML, maximum likelihood.
Fig. 4
Fig. 4. Human genomic analyses.
Analyses are based on the individuals presented here and datasets listed in Supplementary Table 27. a, Principal component analysis (PCA) showing the position of the four individuals analysed among other Indigenous American populations. b, ADMIXTURE analyses (K = 5) for non-Indigenous American sources plus selected representative Indigenous groups from North, Central and South America. c, ADMIXTURE analyses (K = 5) for representative Indigenous groups from North, Central and South America. d–g, F3-statistics of the form F3(outgroup; target, DFU001) (d), F3(outgroup; target, GAP009) (e), F3(outgroup; target, JUC013) (f) and F3(outgroup; target, MXV001) (g) for Indigenous populations of the Americas. Lighter colours represent higher genetic affinity.
Fig. 5
Fig. 5. MCC tree.
The maximum clade credibility (MCC) tree was generated using BEAST 2 under an uncorrelated relaxed clock model based on 2,104 SNPs with fourfold read support and removal of positions with more than 25% missing data in the dataset after exclusion of putative recombinant positions. Coloured bars represent the 95% HPD intervals of dates assigned to each node, with colour indicating the level of posterior support. The red dashed line indicates the year 1492 ce. Asterisks indicate ancient genomes.
Extended Data Fig. 1
Extended Data Fig. 1. Authentication of ancient treponemal DNA in shotgun and capture libraries via DamageProfiler as implemented in EAGER2 via mapping to the human reference genome (left) and T. pallidum pallidum Nichols (right).
Damage signals are predictably low in the partial-UDG treated GAP009 and MXV001 libraries.
Extended Data Fig. 2
Extended Data Fig. 2. Computational screening pipeline for treponemal data processing of modern and ancient datasets.
Image Created in BioRender. Sitter, L. (2024) https://BioRender.com/d39q601.
Extended Data Fig. 3
Extended Data Fig. 3. Coverage of putative virulence-associated genes across the Nichols reference genome (NC_021490.2).
TEN = T. pallidum endemicum, TPE = T. pallidum pertenue, and TPA = T. pallidum pallidum. Genes indicated with an asterisk are reported to be potentially implicated in phenotypic differences between TPE and TPA (supplementary section 11). For additional information on gene coordinates and function, see Table S24.
Extended Data Fig. 4
Extended Data Fig. 4. Bayesian skyline plot showing inferred effective population size (Ne) changes of T. pallidum through time.
The mean estimate and 95% HPD interval are shown. The red dashed line indicates the year 1492 CE.
See this image and copyright information in PMC

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References

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