An antique origin for measles?

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An antique origin for measles?

Since 2018, we are equipped with an ancient DNA (aDNA) lab. We aim at using this facility to study the (more or less) recent evolution of zoonotic agents that succeeded in becoming endemic in human populations. Today, we have released a preprint to report about our first aDNA (actually, aRNA) study!

This first work addresses the timing of measles emergence. Measles is a childhood disease, caused by measles morbillivirus (MeV), which, at least in recent history, has been a heavy burden on human populations. The closest relative of MeV was the rinderpest virus (RPV), a now eradicated pathogen which in the past caused massive die-offs of cattle and wild ungulates. It has long been hypothesized that the progenitor of MeV and RPV infected cattle and - by making the host jump into human populations - gave rise to the MeV lineage. But when did this happen?

It is very hard to answer this question directly. But a relatively popular, indirect way to investigate it, is to determine the divergence date of MeV and RPV - this date provides the lower bound for measles emergence. Recent estimates have consistently pinpointed a very late emergence, with the oldest time to the most recent common ancestor of MeV and RPV falling at the end of the 9th century CE. However, it has also been shown that these estimates - all based on tip-date calibration - were probably biased by substitution saturation and the unaccounted effect of long-term purifying selection.

There are essentially two ways to deal with this problem: extend our temporal sampling of MeV genomes and apply selection-aware molecular clock models. We did both, generating the oldest human RNA virus sequence to date (from a 1912 case) and applying cutting-edge molecular clock models. You can see the details for yourself in the article, but in brief, we found that MeV and RPV probably diverged from each other during the 4th century BCE, i.e. more than 1,000 years earlier than previously thought! Intriguingly, this is about the time when the first human settlements large enough to support continuous MeV transmission appeared. Our results are therefore fully compatible with measles emerging during Antiquity. Definitely proving an antique emergence will require a lot of work and luck since it will only be possible by detecting MeV RNA in antique human remains but now the hunt is officially open! ;-)

This study was only possible by getting an amazing crew together. Thanks a lot for all the good work to our wonderful colleagues of the Charite Museum where the 1912 measles case was found; to those from the Institute of Pathology at Charite who ran the histopathology; to our colleagues from the National Reference Centre for Measles at RKI who provided two additional strains from 1960; to Kyle Harper (University of Oklahoma) who brought his essential insight regarding antique demography; to the team of Philippe Lemey at KU Leuven who co-led this work and together with Marc Suchard (University of California, Los Angeles) imagined the models that ultimately led to these new estimates; and finally to our motivated post-doc associates, students and technical assistants who all committed to running this very nice project on the little free time they have. ;-)

There will be more coming soon from our lab on other early 20th century viruses!