Rabies is a progressively fatal and incurable viral encephalitis caused by a lyssavirus infection. Almost all of the 55 000 annual rabies deaths in humans result from infection with dog rabies viruses (RABV). Despite the importance of rabies for human health, little is known about the spread of RABV in dog populations, and patterns of biodiversity have only been studied in limited geographical space. To address these questions on a global scale, we sequenced 62 new isolates and performed an extensive comparative analysis of RABV gene sequence data, representing 192 isolates sampled from 55 countries. From this, we identified six clades of RABV in non-flying mammals, each of which has a distinct geographical distribution, most likely reflecting major physical barriers to gene flow. Indeed, a detailed analysis of phylogeographic structure revealed only limited viral movement among geographical localities. Using Bayesian coalescent methods we also reveal that the sampled lineages of canid RABV derive from a common ancestor that originated within the past 1500 years. Additionally, we found no evidence for either positive selection or widespread population bottlenecks during the global expansion of canid RABV. Overall, our study reveals that the stochastic processes of genetic drift and population subdivision are the most important factors shaping the global phylogeography of canid RABV.
In 1979, a lineage of avian-like H1N1 influenza A viruses emerged in European swine populations independently from the classical swine H1N1 virus lineage that had circulated in pigs since the Spanish influenza pandemic of 1918. To determine whether these two distinct lineages of swine-adapted A/H1N1 viruses evolved from avian-like A/H1N1 ancestors in similar ways, as might be expected given their common host species and origin, we compared patterns of nucleotide and amino acid change in whole genome sequences of both groups. An analysis of nucleotide compositional bias across all eight genomic segments for the two swine lineages showed a clear lineage-specific bias, although a segment-specific effect was also apparent. As such, there appears to be only a relatively weak host-specific selection pressure. Strikingly, despite each lineage evolving in the same species of host for decades, amino acid analysis revealed little evidence of either parallel or convergent changes. These findings suggest that although adaptation due to evolutionary lineages can be distinguished, there are functional and structural constraints on all gene segments and that the evolutionary trajectory of each lineage of swine A/H1N1 virus has a strong historical contingency. Thus, in the context of emergence of an influenza A virus strain via a host switch event, it is difficult to predict what specific polygenic changes are needed for mammalian adaptation.
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