DNA sequencing is essentially another term for “reading the DNA double helix” or determining the sequence of its nucleotides or bases. Nucleotides are comprised of four chemical bases: adenine (A), thymine (T), cytosine (C), and guanine (G). These bases always form the same base pairs within the DNA double helix: A always pairs with T, and C always pairs with G. This pairing is important for many processes in the cell, including the copying of DNA molecules during cell division. It is also fundamental in DNA sequencing. 

About three billion base pairs of human DNA, the human genome, were sequenced as part of the Human Genome Project (HGP), a collaborative project involving an international team of researchers. The sequencing techniques that were developed to execute the project not only enabled the sequencing of most of the human genome, they also identified and mapped most of the genes within the human genome.

History and Different Types of DNA Sequencing

Allan Maxam and Walter Gilbert developed the first widely adopted method for DNA sequencing in 1973. In 1977, Frederick Sanger and his colleagues developed an alternative method, known as Sanger sequencing or the chain termination method.

Initially, the Maxam-Gilbert method was the more popular method, as purified DNA could be used directly—whereas the Sanger method required cloning to produce single-stranded DNA before sequencing. However, the Maxam-Gilbert method had a number of drawbacks including challenges in scaling up, the exposure of scientists using the method to hazardous chemicals, and technical complexity.

These drawbacks, in combination with the improvement of Sanger sequencing, ensured that Sanger's chain termination method became the most popular of the first generation sequencing methods. It remained widely used, with modifications, for decades.

In the mid-2000s a new kind of DNA sequencing technology known as next generation sequencing (NGS) emerged. It allowed for the sequencing of several DNA molecules in parallel, dramatically increasing the speed of DNA sequencing.

For example, 454 sequencing, one of the first next gen DNA sequencing technologies launched in 2005, made huge advances in terms of the rate of DNA sequencing. Researchers used this technology to sequence the genome of renowned scientist James Watson in just two months. By contrast, the Human Genome Project (HGP), completed in 2003, took 15 years.

The increases in speed and efficiency in sequencing have in turn resulted in much lower costs for the sequencing and analysis of large amounts of DNA. Whereas the cost of the HGP was $3 billion, scientists were able to sequence Watson’s genome for less than $1 million dollars. Today these costs have dropped to approximately $1,000 per genome.

A number of parallel sequencing techniques have been developed following 454 sequencing. While Sanger sequencing is still relatively widely used for smaller scale projects that focus on sequencing individual segments of DNA, today genomes are typically sequenced using these faster, less expensive parallel sequencing methods. And new sequencing methods are emerging all the time as DNA sequencing technologies continue to evolve.

What Does DNA Sequencing Tell Us?

Even though DNA sequencing technology is only about four decades old, its impact on the medical, scientific, and research fields is profound. The implications of DNA sequencing are vast and promising, with a great potential for everything from learning more about your history to diagnostic and therapeutic applications.

The challenge of NGS technologies will be analyzing the large amounts of data that will be available in the coming years as these DNA sequencing technologies become faster and more efficient, generating ever larger amounts of data.