Comparison of genomic DNA sequences: solved and unsolved problems

MOTIVATION: The DNA sequences of entire genomes are being determined at a rapid rate. Whereas initial genome sequencing efforts were for organisms chosen to be widely spaced in the tree of life, there is a growing emphasis on projects to sequence a species that is sufficiently similar to an already-sequenced species to allow direct comparison of those two DNA sequences. This and other changes in genome sequencing strategies have created a strong need for new methods to compare genomic sequences. RESULTS: We sketch the current state of software for comparing genomic DNA sequences and outline research directions that we believe are likely to result in important advances in practice.