Global evolutionary patterns ofYersinia pestisand its spread into Africa

The zoonotic pathogen Yersinia pestis , the etiologic agent of plague, has caused three major pandemics and diversified in different lineages currently established in endemic areas worldwide 1–3 . However, some regions like continental Africa have been poorly covered within the global diversity and epidemiological history of this pathogen 2,4–6 . Here, we report the whole-genome sequences of 1,124 Y. pestis isolates collected from endemic areas worldwide over 116 years, nearly doubling the available genomic data for the species. By integrating population genomics and historical research, we retrace the introduction of multiple Y. pestis lineages into continental Africa, revealing the diversity of the 1.ANT lineage, its historical emergence and its spread to and within Africa since the late 17th century. We identify key mechanisms of genome evolution, including signatures of adaptive evolution present in virulence and biofilm-related genes such as RovA, a master virulence regulator, which likely play a role in the pathogen’s adaptation and endemic persistence. Additionally, our findings reveal an increased trajectory of genome degradation and expansion of IS elements in different lineages. This trend appears especially pronounced in 1.ANT genomes, promoting the remarkable genomic variation within this lineage. Taken together, our findings shed light on the introduction and evolutionary history of plague in Africa and provide a comprehensive framework for understanding the global diversity and genome evolution of Y. pestis , revealing potential factors contributing to its long-term adaptation in endemic areas.