The present invention provides methods for determining sequence similarity (conserved sequences) between nucleic acids from a first organism and nucleic acids from a second, different organism without having to know a priori the nucleic acid sequence from the second, different organism. The first nucleic acid can be from any organism where the sequence of the nucleic acid is known and the second nucleic acid can be from any organism. The method involves determining which bases from the second nucleic acid are identical to the first nucleic acid, and allows one to determine the sequence of portions of the second nucleic acid. The invention is useful for identifying putative functional regions or putative organism-sequences in a genome.