Measles virus and rinderpest virus divergence dated to the sixth century BCE

Abstract

Many infectious diseases are thought to have emerged in humans after the Neolithic revolution. Although it is broadly accepted that this also applies to measles, the exact date of emergence for this disease is controversial. We sequenced the genome of a 1912 measles virus and used selection-aware molecular clock modeling to determine the divergence date of measles virus and rinderpest virus. This divergence date represents the earliest possible date for the establishment of measles in human populations. Our analyses show that the measles virus potentially arose as early as the sixth century BCE, possibly coinciding with the rise of large cities.

Fig. 1.

Formalin-fixed lung specimen collected in 1912 in Berlin from a 2-year old girl diagnosed with measles-related bronchopneumonia (museum object ID: BMM 655/1912).

Fig. 2.. Divergence time estimates for MeV and RPV (red) and for MeV/RPV and PPRV (blue) under increasingly complex evolutionary models.

Estimates for parameters of interest (posterior mean and 95% highest posterior density interval) under each model are provided in table S5.

Fig. 3.. Time-measured evolutionary history for MeV, RPV and PPRV, and largest city size over time in three well-studied regions of the world.

Upper figure displays maximum clade credibility (MCC) tree summarized from a Bayesian time-measured inference using tip-dating and accounting for long-term purifying selection. The red and blue points represent the mean estimates for the divergence times between MeV and RPV and MeV/RPV and PPRV, respectively; the corresponding divergence date estimates are depicted below as marginal posterior distributions. The lower figure represents the estimated size (log10 scale) of the largest city in the western world including Mesopotamia (dark blue), East Asia (teal) and South Asia (green) over time. The red vertical line represents the mean divergence time estimate between MeV and RPV and the red area its 95% highest posterior density interval. The dashed horizontal line represents the classical threshold for MeV maintenance in a population (i.e. 250,000 individuals). Dots show data points according to Morris (34) and Inoue et al. (26). Each line represents the fit of a generalized additive model with a cubic spline smoothing function.