Mutation is the ultimate source of genetic and genomic variation and the relationship between mutation and evolution-
ary change is a fundamental question in biology. Mutations can occur as single nucleotide polymorphisms (SNPs) or
larger structural variants (SVs) like duplications, deletions and copy number variants. Molecular studies have focused
extensively on SNP variation but DNA sequencing technologies are increasingly demonstrating the prevalence and im-
portance of genomic SVs. The recency means that there is little understanding of SVs in evolution and few theoretical
predictions to guide empirical investigations. For example, organisms with holocentric chromosomes, characterized
by diffuse centromeres spread across the length of the chromosome, can have high rates of intrachromosomal
rearrangements and SVs segregating in populations. The sojourn time of a mutation fundamentally affects the
dynamics of natural selection and may differ for SNPs and SVs. Understanding the evolutionary significance of SVs
requires greater understanding of the ways in which population genetic forces of drift, selection and recombination act
on SVs, the long-term outcomes of SVs in genomes and the mechanisms that generate segregating SV mutations.
This application proposes to address these gaps in scientific understanding by addressing 3 questions:
1) What are the population genetics of SV mutations?
2) How do SV mutations accumulate to differences in genome size and content?
3) Does the frequency spectrum of SVs vary between organisms with holocentric and metacentric
To answer these questions my lab group will pursue a synergistic set of theoretical and comparative genomic
projects. We will study a theoretical graph-based model of SVs and formulate a comprehensive population genetic
theory of SV evolution. We will use our theory to formulate predictions regarding SV evolution and test our predictions
by analyzing empirical genomic change in a phylogenetic comparative framework and studying the spectrum of
SVs in holocentric and monocentric organisms. My research program uses an innovative combination of theory
and comparative computational genomics to address fundamental evolutionary questions. The research proposed
here will result in exciting discoveries unlocking the rules of eukaryotic genome evolution.