2020

Research into origins of measles provides insight for dealing with current, future pandemics


UCLA faculty co-led study finds measles appeared in 6th century BCE and is based on the oldest human-infecting RNA virus genome sequenced to date.

DNA

A complex research project designed to answer basic questions about how the human measles virus diverged from a related cattle pathogen has revealed the divergence may have occurred as early as the 6th century BCE, a time where cities were growing and interconnecting, through trade, travel, and war, across Eurasia from China to the Mediterranean.

One of the co-leaders of the project is Dr. Marc Suchard, MD, PhD, professor of Biostatistics, Biomathematics, & Human Genetics at the UCLA Fielding School of Public Health, whose work served as the basis to reassess the divergence date of measles and the related rinderpest viruses. This period – 600 to 501 BCE – marks the earliest possible emergence of the measles virus and was estimated using advanced molecular clock modeling.

“Using computational approaches, we can now account for changing evolutionary dynamics over time. This showed that previous research had substantially underestimated the origin of the measles to the medieval times," said Suchard, who along with colleagues at KU Leuven in Belgium, developed these new models aimed at avoiding such biases.

“Measles appears to have arisen alongside the growth of large and, for the first time, inter-connected cities, which can be directly compared to the situation we face today in regard to emerging infectious diseases, like COVID-19, that arise from zoonotic pathogens,” Suchard said. “Travel between these urban areas took months or years when measles first appeared, but now it takes only hours or day – so we have similar health concerns, but vastly different time-scales.”

The study, published in Science on June 19th, summarizes research from scientists at the Robert Koch Institute (Germany), the KU Leuven (Belgium), the Berlin Museum of Medical History at the Charité (Germany), the University of Oklahoma, and the University of California, Los Angeles (UCLA)

Measles is a highly contagious infectious disease, which despite being vaccine-preventable, still imposes a tremendous burden on human health. Like many human diseases, measles originated in animals. A spill-over of a cattle-infecting virus, the common ancestor to both measles virus and its closest relative rinderpest virus is understood as likely to have given rise to the disease. The timing and circumstances of this important host switch are still debated.

Scientists involved in the current study began by analyzing a formalin-fixed lung from a 2-year-old measles patient who died in 1912 in Berlin, found in the collection of the Berlin Museum of Medical History. The team succeeded in assembling almost the entire measles virus genome - notably, this is the oldest human-infecting RNA virus genome sequenced to date.

“We were thrilled to find that recovery of viral RNA from such an old specimen was possible and, actually, quite an easy thing to do. This opens new perspectives for the study of RNA virus evolution,” said Sébastien Calvignac-Spencer (Robert Koch Institute), whose team sequenced the genome. Thomas Schnalke, the head of the Berlin Museum of Medical History, added: “This underlines the outstanding value of medical specimen collections, which are not only historical but also molecular archives.”

In a second step, the 1912 genome, coupled with already available genomic data from additional measles strains and the related rinderpest and Peste des petits ruminants viruses, served as the basis to reassess the divergence date of measles and rinderpest viruses.

This date was estimated using advanced molecular clock modeling by the teams led by Suchard and Philippe Lemey (KU Leuven); the researchers found the new divergence estimate falls into the 6th century BCE, a period marked by growing populations and the rise of large cities both in Europe and Asia. Measles requires large, connected populations for undisrupted circulation, which likely did not exist prior to this period.

“Of course we cannot say for sure if measles emerged in humans shortly after divergence and if that was linked to demographic change, but it is certainly a plausible scenario that can no longer be excluded,” said Kyle Harper, a historian from the University of Oklahoma.

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Faculty Referenced by this Article

Dr. Marc Suchard
Marc Suchard
Biostatistics
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Damla Senturk
Biostatistics
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Jason H. Moore, Ph.D.
Jason H. Moore

Automated and accessible artificial intelligence methods and software for biomedical data science.

Biostatistics
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Li, Jingyi Jessica
Jingyi Jessica Li
Biostatistics
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David Elashoff
Biostatistics
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Brunilda Balliu headshot
Brunilda Balliu
Biostatistics
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Dr. Weng Kee Wong
Weng Kee Wong
Biostatistics
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Dr. Robert Erin Weiss
Robert Erin Weiss
Biostatistics
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Dr. Donatello Telesca
Donatello Telesca
Biostatistics
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Dr. Dorota Dabrowska
Dorota M. Dabrowska
Biostatistics
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Dr. Jin Zhou
Jin Zhou
Biostatistics
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Dr. Christina Ramirez
Christina Ramirez
Biostatistics
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Dr. Hilary Aralis
Hilary Aralis
Biostatistics
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Thomas Belin
Thomas R. Belin
Biostatistics
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William G. Cumberland
Biostatistics
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Dr. Michele Guindani
Michele Guindani
Biostatistics
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David Gjertson
Biostatistics
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Martin L. Lee
Martin L. Lee
Biostatistics
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Xiaowu Dai headshot
Xiaowu Dai
Biostatistics
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Sean Darling-Hammond
Sean Darling-Hammond
Biostatistics Community Health Sciences
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Dr. Gang Li
Gang Li
Biostatistics
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Dr. Zhe Fei
Zhe Fei
Biostatistics
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Ron Brookmeyer
Ron Brookmeyer
Biostatistics
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Hua Zhou
Hua Zhou
Biostatistics
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Honghu Liu
Biostatistics
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Catherine Ann Sugar
Catherine Ann Sugar
Biostatistics
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Abdelmonem Afifi
Abdelmonem A. Afifi
Biostatistics
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Hyun J. Grace Kim
Biostatistics
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Catherine M. Crespi headshot
Catherine M. Crespi
Biostatistics
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Andrew Holbrook
Andrew Holbrook
Biostatistics
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Sudipto Banerjee
Sudipto Banerjee
Biostatistics
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