An Evolutionary Perspective on the Origin and Spread of Emerging Infectious Diseases

Open Access
Firth, Cadhla Brooke
Graduate Program:
Doctor of Philosophy
Document Type:
Date of Defense:
December 21, 2009
Committee Members:
  • Benjamin Edward Holmes, Dissertation Advisor
  • Andrew Fraser Read, Committee Chair
  • Bryan T Grenfell, Committee Member
  • Anton Nekrutenko, Committee Member
  • Edward C Holmes, Committee Member
  • nucleotide substitution rates
  • codivergence
  • phylogeography
  • DNA viruses
  • RNA viruses
  • emerging infectious diseases
The social and economic burden of emerging infectious diseases is both substantial and increasing. However, relatively little is known of the biological factors that increase the probability of pathogen emergence. A major goal of emerging infectious disease research is to create a framework for predictability that will enable the use of cost effective measures to prevent the future emergence of potentially devastating pathogens, instead of relying on intervention and control. Although the largest class of emerging pathogens is composed of rapidly evolving RNA viruses that infect multiple hosts, we remain a long way from a thorough understanding of the key determinants of disease emergence. The aim of this thesis was to explore the evolutionary dynamics of a broad range of emerging viruses (human and animal, RNA and DNA) in the hope of further revealing the generalities of disease emergence. This thesis tested the validity of the general characterization of RNA viruses as emergent and DNA viruses as existing in codivergent relationships with their hosts. Through rigorous analysis of both the temporal dynamics and phylogenetic structure of hantaviruses (RNA viruses), circoviruses (single stranded DNA viruses) and a variety of double stranded DNA viruses, the studies presented here reveal that viruses with many different genomic structures may be capable of jumping species barriers. Contrary to prior expectation, the rates of evolution in some DNA viruses approached those typically assigned solely to RNA viruses, indicating a similar propensity for genetic variability and adaptability, both key characteristics of emergent pathogens. Further, although many DNA viruses and a few RNA viruses (e.g. hantaviruses) are thought to have codiverged with their hosts, this assumption is usually untested. The rigorous statistical assessment of codivergent evolution applied here to hantaviruses and circoviruses found no evidence for codivergence in either case, indicating that evolution by cross-species transmission may be a general trend of many virus systems, including those with DNA genomes. Finally, this thesis demonstrated the utility of using phylogeographic methods to infer the origins and transmission patterns for viruses spreading rapidly on a global scale, furthering our ability to identify the key determinants of viral emergence.