vonHoldt Lab

Evolutionary Genomics and Ecological Epignomics

Domesticated species were the first genetic model systems, exemplified by classical genetic studies that examined the inheritance of phenotype variants. Yet, the full suite of molecular events that occur during domestication is still unknown. Being among the first domesticated species, canines are an ideal system to study genomic and phenotypic evolution. The domestic dog has a wide range of phenotypic diversity, nearly all of which is lacking in their gray wolf ancestor, and has been the focus of many gene mapping studies that have identified genes of large phenotypic effect as well as disease-associated variants. However, the evolutionary history of these traits has remained largely unexplored. What are the functional molecular changes that occurred during the domestication of the dog? What are the differences in genomic structure and transposon insertion sites found between the domestic dog and gray wolf genomes? Are gene expression differences in dogs associated with phenotypic diversification?

My research interests go beyond the scope of studying DNA variants and include other dimensions of the genome. The convergence of genome technologies and natural history hypotheses sets the stage for exploring traditional questions of behavioral ecology, population biology, and evolutionary history at multiple genomic levels. My research goal is to unravel genotype-phenotype evolution in both a naturally and artificially evolving species. I am specifically interested in the interaction of natural history phenotypes (e.g. social status, pigmentation, disease, fecundity, mating strategy) and gene expression changes and their regulation via epigenetic variation. Chromatin modification, differential methylation, microRNAs, and transcription factor binding can all have a profound effect on gene expression, initiating/silencing transcription, the degree of transcript stability, and splicing. However, epigenomic variation currently remains a largely unexplored area of evolutionary and population dynamics. As such, comparative genomic studies of wild and domesticated species provide the opportunity to integrate DNA-based variants and epigenetic modifications, as well as their potential effects on phenotype diversity. Tracking the inheritance of said variants as well as their evolutionary relationships will provide substantial advances towards understanding phenotype evolution.

My research focus also has an applied perspective as I continue to explore the genomics of the Yellowstone wolf population in collaboration with UCLA and the Yellowstone Wolf Project (National Park Service). Using applied population genomic techniques, this research continues to explore genomic consequences of inbreeding, selection, and disease on this recovering population and conduct pedigree-based studies. Combined with highly detailed and extensive observational data and a great team of National Park wolf biologists, this population is a truly amazing system in which to explore how population ecology impacts genetics.