Plague pathogen population history informed by integrative analysis

NEW YORK – A combination of unstable molecular clocks and slow mutation rates appear to limit the extent to which genetic data Yersinia pestis bacteria alone can be used to unravel the evolutionary dynamics and transmission events behind plague epidemics or pandemics, according to new research from researchers in Canada and Australia.

“You can’t think of plague as a single bacterium. Context is hugely important, as our data and analysis show.“, lead author and correspondent Hendrik Poinar, researcher affiliated with McMaster University and the Canadian Institute for Advanced Research, said in a statement.

As they reported in Communications Biology On Thursday, researchers gathered the whole genome sequences of 601 Y. pestis isolates collected from sites around the world for phylogenetic analysis. They encompassed 540 modern isolates of the microbe as well as 61 ancient strains in an effort to better understand the origins and dynamics of pandemics ranging from the Justinian plague and the medieval Black Death to the so-called third pandemic plague from the 20e century.

Combined with more detailed analyzes of population structure and the molecular clock, the team’s findings highlighted slow evolution in Y. pestis and the instability of the pathogen’s molecular clock, a measure of mutations accumulating over a period of time.

In particular, the authors noted that “a species-wide clock model was methodologically unstable and did not lead to reproducible estimates”.

Given the relatively low substitution rates in the Y. pestis genome, the researchers explained, it may take decades to detect informative lineage-related alterations. Therefore, analyzes based on genetic information alone can lead to misinterpretations when trying to disentangle epidemics and plague dynamics over shorter time periods.

“In isolation, Y. pestis genomic evidence may not be suitable for inferring point migrations and directionality of spread,” the authors reported. “Alternatively, new methods that integrate non-genetic evidence, such as outbreak case records, into phylogeographic analysis present an exciting avenue for interdisciplinary collaboration. , as explicitly integrative models will complement the strength of genetic and historical evidence, while mitigating their respective weaknesses. »

With the help of historical, environmental and cultural clues, the team turned to analyzes specific to the population of the Y. pestis pathogens, which allowed for more accurate profiling of substitution rates, lineage differentiations, geographic origins, and evolutionary histories for the five Y. pestis populations considered.

“Despite this methodological advance, we only obtain robust divergence dates from populations sampled over a period of at least 90 years,” the authors cautioned, “indicating that genetic evidence alone is insufficient to accurately reconstruct the timing and spread of short-term plague epidemics”. .”

With regard to the notorious plague of the Black Death, for example, findings have pointed to culprit pathogens from an ancient lineage with a long history in Europe, dating back decades or centuries. Additionally, the authors argued that “the clonal nature of the Black Death is not an exceptional event, but rather the norm based on the sampling period.”

More broadly, the researchers suggested that a similar integrative approach could provide more informative insights into other plague outbreaks, including those from the past and the future.

“We anticipate that these findings will impact both retrospective and prospective studies of plague, which seek to date the emergence and spread of past pandemics as well as monitor the progress of current epidemics,” wrote authors.

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