DNA sequencing at 40: past, present and future

Abstract

This review commemorates the 40th anniversary of DNA sequencing, a period in which we have already witnessed multiple technological revolutions and a growth in scale from a few kilobases to the first human genome, and now to millions of human and a myriad of other genomes. DNA sequencing has been extensively and creatively repurposed, including as a ‘counter’ for a vast range of molecular phenomena. We predict that in the long view of history, the impact of DNA sequencing will be on a par with that of the microscope. The history and future potential of DNA sequencing, including the development of the underlying technologies and the expansion of its areas of application, are reviewed. This year marks the 40th anniversary of the Sanger method for DNA sequencing, the most widely used sequencing method, pioneered by Fred Sanger and his team in 1977. Jay Shendure and colleagues review the evolution of sequencing technologies since their inception, highlighting the major milestones in the development, analyses and applications of genome sequencing over the past 40 years. Despite multiple technological revolutions and growth in scale, the authors see DNA sequencing as a relatively nascent technology in the grand scheme of scientific history. They review current emerging applications and discuss the continued evolution and future of DNA sequencing from population-scale resequencing to networks of portable sensors used for real-time monitoring in environmental settings.