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Robustness, ecological history, and disease emergence: A study in RNA viruses

Posted on:2010-02-06Degree:Ph.DType:Dissertation
University:Yale UniversityCandidate:Ogbunugafor, Brandon OFull Text:PDF
GTID:1443390002977717Subject:Biology
Abstract/Summary:
150 years after the publication of On The Origin of Species, evolutionary biology continues to grow in scope, sophistication, and relevance. Darwinian evolution's classical axioms are continuously debated and updated, with new technology further refining the lens through which we can observe and understand the evolutionary process. Biomedicine is a relatively recent frontier of Darwinian thinking, promoting the idea that many human illnesses are the product of genetic or physiological conflicts that are best understood from a Darwinian perspective. In particular, the infectious disease paradigm has been strongly influenced by these principles, as breakthroughs in microbial ecology and evolution have improved our understanding of emerging infectious diseases, leading to the implementation of newer, more effective public health practices, and the creation of novel therapeutic regimens.;RNA viruses constitute what many believe to be the greatest single threat to the continued survival of Homo sapiens. Such fears are legitimized by many recent incidents of virulent RNA viral pathogens arising to infect human populations. While obvious characteristics such as short generation time, small genome size, and high mutation rate partly explain RNA virus's proclivity for emerging in human populations, there remain other relatively unexplored details, some of which might be the key to public health solutions that effectively predict and prevent such emergence events.;Here I examine two characteristics of RNA viruses that contribute to their potential to emerge in human populations and further adapt to the pharmacological interventions that we create to suppress them: biological robustness and ecological history. I explore them in two different RNA virus systems: bacteriophage 96 and Vesicular Stomatitis Virus (VSV).;In the case of robustness, I relate genetic robustness to evolvability, and uncover a potential mechanism for this connection. I then explore the relationship between biotic and abiotic environmental robustness, and find that they can be decoupled in RNA virus systems. I then move on to exploring details of niche breadth and ecological generalism, and find that ecological generalists in the RNA virus context tend to adopt a "jack of all trades" phenotype in regards to several characteristics integral to the VSV life cycle: invasion rate, fecundity, and extracellular survivorship. Finally, I combine mathematical modeling with empirical results towards understanding the qualitative and quantitative contributions of important RNA virus characteristics to the probability of emergence. I find that depending on the standard route of transmission, different RNA virus characteristics, such as generalism and extracellular suryivorship, can powerfully influence the probability of emergence of a pathogen.
Keywords/Search Tags:RNA virus, Emergence, Robustness, Ecological, Characteristics
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