MERS-CoV spillover at the camel-human interface

Gytis Dudas; Luiz Max Carvalho; Andrew Rambaut; Trevor Bedford; Ali M. Somily; Mazin Barry; Sarah S. Al Subaie; Abdulaziz A. BinSaeed; Fahad A. Alzamil; Waleed Zaher; Theeb Al Qahtani; Khaldoon Al Jerian; Scott J.N. McNabb; Imad A. Al-Jahdali; Ahmed M. Alotaibi; Nahid A. Batarfi; Matthew Cotten; Simon J. Watson; Spela Binter; Paul Kellam

Observed departures from strictly clonal evolution suggest that while recombination is an issue for inferring MERS-CoV phylogenies, its effect on the human side of MERS outbreaks is minimal, as expected if humans represent a transient host with little opportunity for co-infection. MERS-CoV evolution on the reservoir side is complicated by recombination, though is nonetheless still largely amenable to phylogenetic methods. Amongst other parameters of interest, recombination is expected to interfere with molecular clocks, where transferred genomic regions can give the impression of branches undergoing rapid evolution, or branches where recombination results in reversions appearing to evolve slow. In addition to its potential to influence tree topology, recombination in molecular sequence data is an erratic force with unpredictable effects. We suspect that the effects of recombination in MERS-CoV data are reigned in by a relatively small effective population size of the virus in Saudi Arabia (see next section) where haplotypes are fixed or nearly fixed, thus preventing an accumulation of genetic diversity that would then be reshuffled via recombination. Nevertheless, we choose not to report on any particular estimates for times of common ancestors (tMRCAs), even though these are expected to be somewhat robust for dating human clusters, and we do not report on the evolutionary rate of the virus, even though it appears to fall firmly within the expected range for RNA viruses: regression of nucleotide differences to Jordan-N3/2012 genome against sequence collection dates yields a rate of 4.59 × 10 −4 subs/site/year, Bayesian structured coalescent estimate from primary analysis 9.57 × 10 −4 (95% HPDs: 8.28 − 10.9 × 10 −4 ) subs/site/year.