An Experimental Evaluation of Inversion-and Transposition-Based Genomic Distances through Simulations

Abstract

Rearrangements of genes and other syntenic blocks have become a topic of intensive study by phylogenists, comparative genomicists, and computational biologists: they are a feature of many cancers, must be taken into account to align highly divergent sequences, and constitute a phylogenetic marker of great interest. The mathematics of rearrangements is far more complex than for indels and mutations in sequences. Inversions have been well characterized through 20 years of work, but transpositions still await comparable results. We can compute inversion and DCJ (a combination of inversions and block exchanges) distances, and bounds on the transposition distance. The first has been extensively used in comparative genomics and phylogenetics, the second is quite new, and the third has not seen significant use to date. We present here a detailed experimental study of these three distance measures within the context of genome comparison (pairwise distances) and phylogenetic reconstruction. We used data generated through simulated evolution along various trees, using various evolutionary rates and various mixes of inversions and transpositions. Our main finding is that inversion and DCJ measures return very similar results even on data generated using only transpositions, while the measure based on Hartman's bound is often too loose to provide comparable accuracy in genomic comparisons or phylogenetic reconstruction