We are evolutionary biologists largely focused on understanding the processes and mechanisms underlying adaptation, especially for traits mediating antagonistic interactions between hosts-pathogens and predators-prey. Our evolutionary genomic research involves generating genomic, transcriptomic, proteomic, epigenomic, and functional genomic data, and we often integrate these data with field ecology, morphology, and other diverse data types to address broad biological questions. Although most of our research focuses on (1) Tasmanian devils and a species-specific transmissible cancer, and (2) venomous snakes and what they eat, we are interested in working in other systems that also enable us to learn more about the adaptive process in natural populations. Examples of current research projects in the lab are described below.
Emerging infectious diseases (EIDs) are the sixth leading cause of species' declines and threaten human, wildlife, and livestock health. A remarkable example of a wildlife EID is devil facial tumor disease (DFTD), a transmissible cancer that has had devastating effects on the Tasmanian devil. Devils with strange facial tumors were first discovered in 1996 in northeastern Tasmania, and later studies showed that the cause was a clonal cell line and, therefore, a transmissible cancer. Since then, DFTD has spread nearly 95% of the way across Tasmania, caused localized declines exceeding 90%, and reduced the total population size by roughly 80%. Devils show high susceptibility to DFTD, which appears nearly always fatal within six months from first clinical symptoms. Early epidemiological models predicted extirpation in long-diseased populations, but these populations continue to persist. We study the genetic basis of disease-related phenotypes in both the Tasmanian devil and DFTD to better understand host-pathogen interactions and disease dynamics.
Genetic basis of disease-related traits
Identifying the genetic architecture of complex phenotypes, particularly for disease-related traits, is a central goal of modern biology. We use genome-wide associations and other comparative genomic approaches to identify the genetic basis of disease-related phenotypes in both Tasmanian devils (e.g., survival following infection) and DFTD (e.g., tumor regression). Functional genomics are often used to validate specific variants of interest. The Margres lab, in collaboration with Dr. Andrew Storfer, Dr. Menna Jones, and Dr. Hamish McCallum, was awarded a National Science Foundation Grant in 2020 (NSF DEB 2027446), to (1) explore genotype-by-genotype interactions between hosts and tumors underlying specific coevolving traits, and (2) determine how these interactions affect disease outcomes and community dynamics.
Epistasis and genomic complexity
Adaptation dynamics dictate the rate and predictability of evolution, but phenomena such as epistasis may increase variation in evolutionary outcomes and, therefore, reduce predictability unless we can begin to identify general patterns of epistatic interactions. Because recombination does not break up linkage between mutations in asexual populations such as DFTD, the fates of particular mutations are not independent. We are interested in characterizing epistasis and other genetic phenomena in DFTD and determining how these factors affect cancer evolution.
Snake venoms have emerged as a system for studying the adaptive impacts of phenotypic variation in polygenic traits because of their genetic tractability, contributions to fitness, and high evolutionary rates. Snake venoms are comprised of 5–25 toxin-gene-families that show extreme levels of expression divergence and sequence evolution across multiple phylogenetic scales. We use this genetic tractability to link the patterns of venom variation to specific genetic mechanisms to better understand the process of adaptive evolution.
Venom divergence, however, is only half of the story. Because snake venoms function solely following injection into another organism, prey provide geographically variable selective pressures through their own genetic variation. Selection can vary among interacting populations as a result of genotype-by-genotype-by-environment interactions, producing phenotypic variation because locally beneficial traits are not expected to become fixed at the species level. As a result, we are also interested in identifying the genetic basis of venom resistance in prey and determining how one trait may bias the evolution of the other at the molecular level.
Mechanisms underlying adaptive variation
Venom exhibits exceptional levels of variation across species, within species, and even within an individual over its lifetime. Ultimately understanding what these patterns of variation tell us about the process of adaptation requires an understanding of the genetic mechanisms underlying this variation. Much of our work uses the genetic tractability of the venom system to (1) identify the specific genetic mechanisms generating variation in this complex phenotype, and (2) determine whether biases in these mechanisms can allow us to make predictions regarding the process of adaptation in polygenic traits.
Multiple species of prey have been shown to exhibit varying levels of resistance to snake venoms. Yet recent work has found that venomous snakes are consistently "winning" the predator-prey arms race despite longer generation times, smaller effective population sizes, and presumably weaker selection as outlined by the Life-Dinner Principle. We work with populations of venomous snakes and their prey across multiple island sites in the southeastern United States to better understand this paradox from ecological, evolutionary, and genomic perspectives.
Island biogeography and trait evolution
The Margres Lab, in collaboration with Dr. Jason Strickland, Dr. Chris Parkinson, Dr. Miguel Borja, Hector Franz of HerpMX, and Alexandra Rubio Rincón, was recently awarded an Exploration Grant from the National Geographic Society (NGS-61140R-19) to determine whether venom complexity co-varies with specific habitat characteristics. The project focuses on island populations of rattlesnakes in the Sea of Cortéz. By using islands as a proxy for fragmented environments, our work will explore how trait evolvability affects extinction, migration, and persistence. Read about the project here.