From Packrats to Pandemics: Evolution and Diversity of Viruses and Their Mammalian Hosts

Abstract

Viruses are ubiquitous, obligate parasites that infect all forms of life. Despite their ubiquity and importance however they are mainly studied only in the contexts where they cause human disease. Most human viruses come from spillover events from other animals, therefore from a human-health standpoint it is paramount to better understand the evolution and distribution of viruses as they occur in wild mammals. The primary goal of the research presented here is thus to understand evolutionary patterns of viruses in wild mammals, especially bats and rodents. To do this, viruses were sequenced with a variety of techniques and sources, and analyzed using phylogenetic methods to understand host diversity, host specificity, and codivergence with their hosts. Ancient DNA was extracted from ancient packrat middens, from which I show the presence of papillomavirus DNA from 27,000 year samples. This, combined with a significant signal of codivergence between rodents and papillomaviruses, suggests these hosts and viruses have a shared evolutionary history of at least 17 million years. Next, to study viral diversity in a modern context, I sampled 358 individual small mammals from 15 rodent and 18 bat species. I screened these samples with degenerate paramyxovirus primers to amplify a sequence fragment that could be used for phylogenetic analysis. Next, from these positives I selected a subset and attempted to recover whole genome sequences using de novo RNA-seq. A total of five near full length paramyxovirus genomes were recovered. These genomes were used to better understand genome evolution and host receptor binding in a larger global context of paramyxovirus evolution in concert with previously described paramyxovirus genomes from small mammals. To expand our knowledge of rodent diversity, population isolation, and evolution in Arizona, I sampled Peromyscus individuals at the top of three sky islands in SE Arizona. I show these individuals belong to Peromyscus melanotis, a species thought to mainly inhabit the Sierra Madre in Mexico. With molecular clock analysis based on rates of cytochrome B evolution, I show these sky island populations have been isolated since the last ice age, ~11,000-55,000 years ago. Finally, due to the emergence of a SARS-CoV-2 pandemic during the final year of my study, I was able to apply phylogenetic methods to better understand a human spill-over event as it was happening in the present day. Here I tracked the early spread and introduction of the pandemic in Arizona with a large collaboration of people from other Arizona research institutes. In summary, this dissertation provides important insight into the shared evolutionary history of viruses and their mammalian hosts.