Diseases do not affect all individuals in the same way. Why does one animal get sick, when another, exposed to the same environmental conditions, remains healthy? Answering this question offers a central challenge in disease ecology. The answer may lie in differences in genetic make-up of individuals. Some individuals have a greater diversity of alleles than other individuals do. Evidence from inbred populations suggests that an individual's genetic diversity might be associated with reduced levels of parasitism, but this relationship has never been examined in a large, natural population. This research will address two questions. Does genetic diversity enhance an individual's ability to resist parasites? How important is the effect of genetic diversity relative to the many other factors that are also known to be strong predictors of parasitism? These questions will be addressed by generating genetic and parasite profiles for individual animals from a large, well-studied, animal population. Statistical models will be used to assess the importance of genetic variability in determining parasite burdens.
Human welfare depends in a way that is truly fundamental on a basic understanding of the factors that control disease. This research will enhance understanding of the role of genetics in controlling resistance to parasitism. A post-doctoral student and undergraduate students will be trained.
There is a great deal of interest within the scientific community in the relative role of genetic variability in successfully overcoming exposure to pathogens. The primary intellectual merit goal of this research was to better understand the relationships between genetic variability and the extent to which an individual animal is parasitized. To conduct this work, research was conducted on four related themes: describing relationships of neutral genetic variability and host parasitism; describing the structure of an important major histocompatibility complex gene (MHC-DRB exon 2) that is thought to be associated with immunocompetence, in the focal host species; describing how MHC variability of hosts influences measures of parasitism; contrasting the relative importance of neutral, MHC, and non-genetic factors underpinning our ability to predict the likelihood and extent of parasitism of individual host animals. Our results suggest that even in large populations of animals for which inbreeding is generally not thought to be a concern, animals with lower levels of genetic variability and those with slightly higher measures of inbreeding are less likely to successfully mount an immune response when challenged by highly pathogenic viruses. Thus our results expand the recognized importance of genetic variability beyond the realm of populations that have been subjected to reductions in genetic variability to include large populations with a full range of genetic variability. Furthermore, our results indicate that there is strong selection acting on MHC loci. We observed that while the role of MHC in relation to other genetic, demographic, and ecological factors depends on the pathogen of interest, it may be one of the most important factors predicting successful immune response. We observed that particular MHC alleles were associated with having antibodies to particular viruses. The broader impacts of this project provided training to three post-doctoral associates and multiple undergraduates. Each of the post-doctoral associates gained experience and training in field techniques (in particular, noninvasive monitoring of animals and animal handling), in laboratory genetic techniques and associated data analyses (in particular, next-generation sequencing), in grantsmanship, and in writing (working with the Principal Investigators to author manuscripts). Each of the post-doctoral associates also gained some teaching and mentoring experience by giving guest lectures in undergraduate courses and working with undergraduate students involved with the project. Undergraduate students involved with the project gained insights into field experiments, experimental design, non-invasive monitoring of wildlife, and dietary and parasite analyses, and laboratory genetic methodologies.
