Estimation of the true evolutionary distance under the fragile breakage model

Nikita Alexeev, Max A. Alekseyev

The ability to estimate the evolutionary distance between extant genomes plays a crucial role in many phylogenomic studies. Often such estimation is based on the parsimony assumption, implying that the distance between two genomes can be estimated as the rearrangement distance equal the minimal number of genome rearrangements required to transform one genome into the other. However, in reality the parsimony assumption may not always hold, emphasizing the need for estimation that does not rely on the rearrangement distance. The distance that accounts for the actual (rather than minimal) number of rearrangements between two genomes is often referred to as the true evolutionary distance. While there exists a method for the true evolutionary distance estimation, it however assumes that genomes can be broken by rearrangements equally likely at any position in the course of evolution. This assumption, known as the random breakage model, has recently been refuted in favor of the more rigorous fragile breakage model postulating that only certain "fragile" genomic regions are prone to rearrangements. We propose a new method for estimating the true evolutionary distance between two genomes under the fragile breakage model. We evaluate the proposed method on simulated genomes, which show its high accuracy. We further apply the proposed method for estimation of evolutionary distances within a set of five yeast genomes and a set of two fish genomes. The true evolutionary distances between the five yeast genomes estimated with the proposed method reveals that some pairs of yeast genomes violate the parsimony assumption. The proposed method further demonstrates that the rearrangement distance between the two fish genomes underestimates their evolutionary distance by about 20%. These results demonstrate how drastically the two distances can differ and justify the use of true evolutionary distance in phylogenomic studies.