A computer implemented method for generating nucleotide sequences containing candidate homing endonuclease genes (HEGs). A search is performed in a database stored on a storage medium of nucleotide sequences for amino acid sequences having a subsequence having a homology level with the translation of a subsequence of one or more predetermined HEGs. For each amino acid sequence generated by the search, one or more nucleotide sequences are retrieved encoding the amino acid sequence. The results of this search used in a second search of a database stored on a storage medium to generate the HEG containing sequences.