Partially local three-way alignments and the sequence signatures of mitochondrial genome rearrangements.

BACKGROUND

Genomic DNA frequently undergoes rearrangement of the gene order that can be localized by comparing the two DNA sequences. In mitochondrial genomes different mechanisms are likely at work, at least some of which involve the duplication of sequence around the location of the apparent breakpoints. We hypothesize that these different mechanisms of genome rearrangement leave distinctive sequence footprints. In order to study such effects it is important to locate the breakpoint positions with precision.

RESULTS

We define a partially local sequence alignment problem that assumes that following a rearrangement of a sequence , two fragments , and are produced that may exactly fit together to match , leave a gap of deleted DNA between and , or overlap with each other. We show that this alignment problem can be solved by dynamic programming in cubic space and time. We apply the new method to evaluate rearrangements of animal mitogenomes and find that a surprisingly large fraction of these events involved local sequence duplications.

CONCLUSIONS

The partially local sequence alignment method is an effective way to investigate the mechanism of genomic rearrangement events. While applied here only to mitogenomes there is no reason why the method could not be used to also consider rearrangements in nuclear genomes.