Chromosomal breakpoint re-use in the inference of genome sequence rearrangement

In order to apply gene-order rearrangement algorithms to the comparison of genome sequences, Pevzner and Tesler [9] bypass gene finding and ortholog identification, and use the order of homologous blocks of unannotated sequence as input. The method excludes blocks shorter than a threshold length and ignores small block-internal rearrangements. Here we investigate possible biases introduced by eliminating and amalgamating short blocks, focusing on the notion of "breakpoint re-use" introduced by these authors. Analytic and simulation methods show that re-use is very sensitive to threshold size and to parameters of the rearrangement process. As is pertinent to the comparison of mammalian genomes, large thresholds in the context of high rates of small rearrangements risk randomizing the comparison completely. We suggest a number of mathematical, algorithmic and statistical lines for further developing the Pevzner-Tesler approach.