Estimation of Rearrangement Break Rates Across the Genome

Abstract

Genomic rearrangements provide an important source of novel functions by recombining genes and motifs throughout and between genomes. However, understanding how rearrangement functions to shape genomes is hard because reconstructing rearrangements is a combinatoric problem which often has many solutions. In lieu of reconstructing the history of rearrangements, we answer the question of where rearrangements are occurring in the genome by remaining agnostic to the types of rearrangement and solving the simpler problem of estimating the rate at which double-strand breaks occur at every site in a genome. We phrase this problem in graph theoretic terms and find that it is a special case of the minimum cover problem for an interval graph. We employ and modify existing algorithms for efficiently solving this problem. We implement this method as a Python program, named BRAG, and use it to estimate the break rates in the genome of the model Ascomycete mold, Neurospora crassa. We find evidence that rearrangements are more common in the subtelomeric regions of the chromosomes, which facilitates the evolution of novel genes.