James Ruff

Email: j.ruff@utah.edu

The primary goal of my research platform is to apply common techniques of evolutionary biology to questions concerning human health. Specifically, I seek to quantify the ultimate-level health effects of experimental exposures by measuring the Darwinian fitness (lifetime reproduction) and its key components (social dominance and survival) in experimental and control mice in a model system referred to as Organismal Performance Assays (OPAs). My first work in this area was on health consequences of added-sugar consumption (Ruff et al. 2013). Here, we demonstrated that human-relevant levels of added sugar consumption increased female mortality 2-fold and decreased male reproduction by 25% relative to mice fed a starch-based control diet. Additionally, males fed the added sugar diet were also less likely to posses a territory and become socially dominant. These findings represent the lowest level of sugar consumption shown to adversely affect mammalian health and indicate that the health effects of added sugar consumption at levels consumed by a quarter of Americans may be more damaging to health than previously thought. Furthermore, these findings point out shortcomings in our current mechanistic understanding of how added sugar consumption causes disease because common clinical measures where not predictive of ultimate-level findings revealed in OPAs.

A second focus of my research platform speaks to the question of how long-lived, slow evolving organisms like vertebrates are not overwhelmed and obliterated by the evolutionary potential of pathogens. I have helped design and conduct experimental evolution studies which show that pathogen (Friend Virus Complex) adaptation produces trade-offs that result in pathogen fitness being higher in hosts (mice) with familiar MHC genotypes, as compared to those with unfamiliar MHC types; this adaptation produces correlated patterns of virulence (Kubinak et al. 2012). This work is unique because it experimentally supports the requisite conditions of the Red Queen model of MHC evolution and provides quantification of fitness effects for both pathogen and host. Additionally, we demonstrate that MHC polymorphisms, as opposed to other polymorphisms across the genome, account for the majority of the total observed reductions in viral fitness and virulence in unfamiliar host genotypes. Our findings suggest that the MHC is a major host factor within vertebrates for influencing pathogen adaptation and virulence evolution (Kubinak et al. 2013).