# Whole-genome sequencing reveals evidence for inter-species transmission of the yaws bacterium among nonhuman primates in Tanzania

## TL;DR

Whole-genome sequencing of yaws bacteria in Tanzanian nonhuman primates reveals recent inter-species transmission events.

## Contribution

Evidence of recent inter-species transmission of TPE among nonhuman primates in Tanzania is presented through genome comparisons.

## Key findings

- Five genome comparisons showed high genetic similarity across different NHP species, suggesting inter-species transmission.
- Estimated substitution rate of TPE in NHPs is between 1.77 × 10-7 and 3.43 × 10-7 per site per year.
- Inter-species transmission events are predicted to have occurred recently, within decades.

## Abstract

Treponema pallidum subspecies pertenue (TPE) is the causative agent of human and nonhuman primate (NHP) yaws infection. The discovery of yaws bacterium in wild populations of NHPs opened the question of transmission mechanisms within NHPs, and this work aims to take a closer look at the transmission of the disease.

Our study determined eleven whole TPE genomes from NHP isolates collected from three national parks in Tanzania: Lake Manyara National Park (NP), Serengeti NP, and Ruaha NP. The bacteria were isolated from four species of NHPs: Chlorocebus pygerythrus (vervet monkey), Cercopithecus mitis (blue monkey), Papio anubis (olive baboon), and Papio cynocephalus (yellow baboon). Combined with previously generated genomes of TPE originating from NHPs in Tanzania (n = 11), 22 whole-genome TPE sequences have now been analyzed. Out of 231 possible combinations of genome-to-genome comparisons, five revealed an unexpectedly high degree of genetic similarity in samples collected from different NHP species, consistent with inter-species transmission of TPE among NHPs. We estimated a substitution rate of TPE of NHP origin, ranging between 1.77 × 10-7 and 3.43 × 10-7 per genomic site per year.

The model estimations predicted that the inter-species transmission happened recently, within decades, roughly in an order of magnitude shorter time compared to time needed for the natural diversification of all tested TPE of Tanzanian NHP origin. Moreover, the geographical separation of the sampling sites (NPs) does not preclude TPE transmission between and within NHP species.

Treponema pallidum subsp. pertenue (TPE) is the causative agent of neglected tropical disease yaws. This bacterium infects humans in endemic regions in Africa, southern Asia and the Pacific region, and NHPs in Sub-Saharan Africa. The infection manifests as papillomas and/or ulcers, and can progress into deformation of bone and cartilage if untreated. Yaws is targeted by the currently ongoing second yaws eradication campaign, known as the Morges strategy, led by World Health Organization (WHO). In this work, we studied the transmission of the yaws bacterium in wild populations of NHPs, as they could serve as a possible source of reinfection of humans in the future, post-yaws eradication in humans. We have determined eleven whole TPE genomes from NHPs from different national parks in Tanzania. Together with previously determined genomes, we have analyzed 22 sequences, and we found a high degree of genetic similarity in samples isolated from different NHP species. This similarity is consistent with inter-species transmission of TPE among NHPs.