In 1977, bacteriophage phi-x174 (5386bp) became the first organism to be sequenced completely, by Sanger and colleagues [Nature 246, 687 (1977)]. In 1982, bacteriophage lambda (48,502bp) was completed using a strategy based on sequencing random fragments of DNA, in this case produced by digesting the lambda genome with restriction enzymes, again by Sanger and colleagues [J. Mol. Biol. 162, 729 (1982)].

Thirteen years elapsed before the first nonviral organism was sequenced completely, this time using whole-genome random sequencing and assembly, called shotgun sequencing. In July1995, Fleischmann and colleagues reported the completion of Haemophilus influenzae (1,830,137bp), the first free-living organism to be sequenced [Science 269, 469 (1995)]. At the end of 1995, the complete DNA sequence of Mycoplasma genitalium (580,070bp), another free-living organism, was published by Fraser and colleagues. M. genitalium DNA encoded only 470 predicted ORFs, providing an estimate for the minimal number of genes needed to support life [Science 270, 349 (1995)].

Since 1995, complete genomic sequences have been published or made available for four more organisms: Methanococcus jannaschii, an Archaeon; Synechosystis, a cyanobacterium species; Mycoplasma pneumoniae, a eubacterium closely related to M. genitalium; and the yeast Saccharomyces cerevisiae, the first eukaryotic organism to be completely sequenced.