40 years of Sanger sequencing

DNA sequencing has a remarkable history, in terms of inception and evolution of the technologies themselves, as well as the breadth and scope of problems to which they have been applied. This Nature collection celebrates 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.

In a Review and accompanying Milestones, Jay Shendure, Shankar Balasubramanian, George M. Church, Walter Gilbert, Jane Rogers, Jeffery A. Schloss and Robert H. Waterston review the evolution of sequencing technologies over the past 40 years. The Milestones list key advances in methods development, computational analyses and applications of genome sequencing. We also highlight a selection of key publications from these Milestones that appeared in Nature journals in the Methods, Genomes and Applications sections.

Accompanying news and commentary in Nature bring further perspectives on this 40 year anniversary of Sanger sequencing. In a Commentary Eric Green, Eddy Rubin and Maynard Olson share perspectives on the future of sequencing over the next 40 years. A Technology Feature explores recent progress in one emerging method, nanopore sequencing, showing potential to upend the DNA sequencing market. A News Feature provides context on genomics applications in direct to consumer genetic testing.

- Orli Bahcall, Senior Editor, Nature

LISTEN: Nature Podcast with NHGRI Director Eric Green on how DNA sequencing has transformed biology, and what might still be to come.

Milestones in computational methods 

The milestones listed below correspond to key developments in the new computational tools and bioinformatics methods for processing and analyses of sequencing data. This is a large area and we apologize for any omissions.


1981: Smith–Waterman

1982: GenBank/ENA/DDBJ 

1990: BLAST

1995: TIGR assembler

1996: RepeatMasker


1998: phred, phrap, consedphred introduced quantitative, reliable metrics for base quality, substituting human judgement with computers, a process that occurred repeatedly over the course of the Human Genome Project.

2000: Celera assembler

2001: Bioconductor

2001: EULER

2002: BLAT

2002: UCSC Genome Browser

2002: Ensembl

2005: Galaxy

2007: Short Read Archive (SRA) / European Nucleotide Archive (ENA) / DDBJ


2008: Velvet

2009: Bowtie

2009: BWA

2009: SAMtools

2009: BreakDancer

2009: Pindel

2009: TopHat

2010: SOAPdenovo

2010: GATK

2010: Cufflinks

2011: Integrated Genomics Viewer

2013: HGAP/Quiver

2017: Canu