Rise of the Machines

Until recently, sequencing the entire genome of an organism was a major endeavor. New technologies are transforming this task into routine practice and launching a new assault on whole-genome sequencing. It is more than 30 years since Sir Fred Sanger and colleagues published their method for sequencing DNA [1]. This Nobel Prize–winning work formed the basis of the vast majority of subsequent sequencing methodologies, albeit with some crucial technical innovations. Despite the great utility of Sanger sequencing, its scalability is inherently limited, and therefore the creation of warehouse-sized facilities was required to accomplish whole-genome sequencing projects. As a result, sequencing more than a few kilobases of DNA—a requirement for all but the simplest genomes—has long remained the province of a few dedicated sequencing centers. Within the last year, however, things have begun to change in dramatic ways. New sequencing technologies are emerging, announced in an assortment of reports, conference presentations, and press releases. In this issue of PLoS Genetics, Srivatsan et al. [2] report the resequencing of several genomes of the bacterium Bacillus subtilis using one of these new technologies. A new battle at the frontier of DNA sequencing has commenced.