Attenuation of virulence in Yersinia pestis across three plague pandemics

Yersinia pestis has spilled over from wild rodent reservoirs to commensal rodents and humans causing three historically recorded pandemics. Depletion in the copy number of the plasmid-encoded virulence gene pla occurred in later-dated strains of the first and second pandemics, yet the biological relevance of the pla deletion has been difficult to test. We identified modern Y. pestis strains that independently acquired the same pla depletion as ancient strains, and herein show that excision of pla from the multi-copy pPCP1 plasmid is accompanied by the integration of a separate full pPCP1 harboring pla into the single-copy pCD1 plasmid, reducing pla dosage. Moreover, we demonstrate that this depletion decreases mortality of mice in models of bubonic plague, but not in the pneumonic and septicemic forms of the disease. We hypothesize that pla depletion may have been selectively advantageous in bubonic plague due to rodent fragmentation following pandemic-induced mortality., , , # Attenuation of virulence in *Yersinia pestis* across three plague pandemics

[https://doi.org/10.5061/dryad.xksn02vs1](https://doi.org/10.5061/dryad.xksn02vs1)

## Description of the data and file structure

Supplementary figures have been uploaded as individual .PDF files and their figure captions are listed below. Data files have been uploaded within a single excel file, descriptions/titles for each table are listed below. The filtered multiple sequence alignment of 317 *Y. pestis* samples used to create Figure 1 and Fig. S5 and its description are also listed below. For detailed methodology please refer to the materials and methods section of the manuscript. 

Figures were made using R-studio, Geneious, and BioRender, and Mummerplot. Edits were made in Adobe Illustrator. 

### Files and variables

#### File: raw\_chromosome.snps.filter5.aln

**Description:** Filtered multiple sequence alignment of 317 *Y. pestis* samples. Alignment file for a maximum likelihood phylogenetic analysi...,