Grant: Discovery Grants Program - Individual

Viruses evolve rapidly, in part because of their high mutation rates and short generation times. In addition, many viruses have compact genomes that encode the necessary functions to exploit a host environment using as little as ~2,000 nucleotides. The selection for compact genomes is evidently so strong that overlapping reading frames (OvRFs) are ubiquitous in viruses. Nevertheless, virus genomes are diverse in their length and composition, and can evolve within directly observable time scales even within a single host infection and many genomic polymorphisms can confer a host--specific selective advantage for the virus. However, we understand little about how virus genomes evolve. Are sequence insertions influenced by the nucleotide composition of the virus genome? What are the effects of selection on rates of evolution within overlapping reading frames? How often do new virus genes arise within reading frames, and how long do they persist before deteriorating under constant mutation? My proposed research program will develop new computational and phylogenetic methods to address these basic questions about the evolution of virus genomes. First, we will develop empirical models of insertions and then use these models to determine whether insertions are shaped by the ancestral sequence, and how new insertions are filtered by selection. Second, we will develop simulation-based methods to determine the effect of selection on rates of evolution within overlapping reading frames in virus genomes, and use this information to date the origin of ancient virus lineages. Third, we will adapt gene detection methods to identify potential new genes and overlapping reading frames in viruses, and then estimate the rates of gene birth and death from a comparative analysis of virus genomes.