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Aim. The present paper provides a comparative analysis of the phylogenetic relationship between Yersinia pestis strains isolated in the Volga-Ural sandy natural focus during the periods of 1912-1945 and 1963-2003, which were characterised by different levels of epidemic activity, in order to identify the spatiotemporal patterns in the circulation of the plague pathogen in the North Caspian region. Materials and methods. We studied the properties and performed whole-genome sequencing of 18 Y. pestis strains from the Volga-Ural sandy focus, along with 12 strains from other foci in the North Caspian and North Aral regions, isolated from 1912 to 2003. The phylogenetic analysis was performed drawing on the whole-genome SNP analysis, which was conducted on the basis of 2188 SNPs identified in the core genome using the Wombac 2.0 program. Maximum Likelihood Dendrogram (GTR model) was used for the analysis of phylogenetic relationships between strains. Results and discussion. All studied strains from the foci of the North Caspian region belong to the main subspecies (biovar medievalis) of the plague pathogen. These are highly virulent and epidemiologically dangerous strains. The whole-genome sequencing and phylogenetic analysis of 30 strains from the Volga-Ural sandy focus, as well as adjacent plague foci, reveal that the strains (biovar medievalis) of two phylogenetic branches - 2.MED4 and 2.MED1 - were spread across the focus under study in the early 20th century. It is confirmed that 2.MED1 strains were the etiological agents of plague outbreaks in the Volga-Ural sandy focus during this period. The study revealed the presence of parallel evolutionary lines in 2.MED1 associated with plague outbreaks in the first half of the last century. In the second half of the 20th and early 21st centuries, the modern evolutionary line of 2.MED1 became widespread in the Volga-Ural sandy focus. The strains of this line are closely grouped, which indicates their close genetic relationship. Only sporadic cases of plague were recorded during this period. Modern strains from the Volga-Ural sandy focus (1963-2003), as well as the strains previously isolated there (1912-1945), do not originate from each other. These strains represent closely related, independent evolutionary branches, extending from the common trunk of 2.MED1. Modern strains originating from those of the North Aral desert focus (1945) form a separate cluster in the dendrogram. This suggests that, following a break in the 1950s, the Volga-Ural sandy focus was recolonised by closely related strains from the North Aral region.