Jasons's CV


Jason Kubinak

Email: jason.kubinak@utah.edu

Co-evolving pathogens are potent selective forces operating on their host populations. The co-evolutionary arms race hypothesis (CARH) posits that heritable genetic variability in both pathogen and host populations can be continuously produced and maintained over evolutionary time through successive rounds of adaptation and counter-adaptation between co-evolving antagonists (Van Valen, 1973). Indeed, the multiple examples of MHC-dependent immune evasion by viruses (Bertoletti et al., 1995; Moskophidis and Zinkernagel, 1995; Jeffery et al., 1999) provide evidence for the existence of such an evolutionary process. Multiple biological phenomenon have been at least partially explained as the result of co-evolutionary arms race dynamics including the emergence of infectious diseases (Thorne and Williams, 1988; Roelke-Parker et al., 1996; Altizer et al., 2003), autoimmunity (Fujinami et al., 2006), rapid diversification of certain immune system genes (Borghans et al., 2004), the evolution of elaborate secondary sexual characters (Hamilton & Zuk, 1982), and even the evolution of sexual reproduction itself (Hamilton et al., 1990). Surprisingly however, there have been few rigorous tests of this hypothesis’ most fundamental prediction; that pathogen adaptation is host-genotype specific.

Experimental pathogen evolution (whereby a pathogen is passaged through successive host organisms) is a powerful tool for dissecting co-evolutionary relationships between hosts and their pathogens. Numerous studies using this experimental design have demonstrated that pathogens are capable of rapidly adapting both greater reproductive output and virulence in their host-of-passage (Ebert, 1998). My work involves using experimental pathogen evolution to test the predictions that pathogen adaptation is host-genotype specific and that genetic variability within host populations impedes pathogen adaptation. Since immunoselection is predicted to be stronger on pathogens producing chronic versus acute infections we chose a chronic mouse-specific pathogen (Friend murine leukemia virus complex (F-MuLV)) as our disease model. Briefly, F-MuLV was serially passaged through ten individual mice from each of 6 different congenic mouse lines and viral titers (as well as disease severity) produced by pre-passage virus stock was compared with post-passage virus stocks. My preliminary work suggests that pathogen fitness increases across serial passage and that the extent of fitness gains is strongly dependent upon the host genotype of passage. Further experiments testing that pathogen adaptation is genotype-specific, and that host genetic heterogeneity impedes pathogen adaptation are ongoing.

From an applied perspective, a better understanding of pathogen adaptation is important for vaccine development through creation of attenuated vectors and the prevention of pathogen escape from vaccine-stimulated immunity (Goulder and Watkins, 2004; Sanjuan et al., 2007). Additionally, many vertebrate farm animals and all endangered species have reduced genetic diversity. Therefore, any breeding program designed to limit the damage of infectious diseases on these species must be based on understanding the role of host genetic diversity in impeding pathogen adaptation. Selective breeding for resistant individuals in domestic livestock may reduce our dependence on antibiotics, which would help slow the emergence and spread of resistant pathogens (Khachatourians, 1998). Furthermore, if we could identify what constituted “critical” host genetic diversity with respect to impeding pathogen adaptation it may be possible to breed for resistance in endangered captive-bred animals as well as increase the proportion of resistant genotypes in re-introduced founder populations of endangered species.

My work is currently supported by the NIH-funded Microbial Pathogenesis Training Grant.