Abstract: A method and computer-program product for sequencing nucleic acid sequences using restriction fragment maps derived from end-sequenced nucleotide fragments. The initial nucleotide sequence can be processed to form a shot-gun-data set. The present teachings employ a technique called Restriction Site Shotgun Sequencing (RSSS.) It can reduce the amount of overlap required between fragment ends while still producing a good assembly. A decrease in overlap can be achieved by using additional information in the fragments to assist in determining that two fragments overlap.