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Third generation sequencing

With third generation sequencing, sequencing a genome has become a cheaper, faster and more sophisticated process. 

Since Human Genome Project, the cost of sequencing genomes has decreased more than a thousand-fold.

Since the Human Genome Project the development of newer and better DNA sequencing technologies has led to the cost of sequencing genomes decreasing more than a thousand-fold. No sooner had next-generation sequencing reached the market than a third generation of sequencing was being developed. 

SMRT enables scientists to effectively ‘eavesdrop’ on DNA polymerase.

One of these new technologies was developed by Pacific Biosciences and is called Single-Molecule Sequencing in Real Time (SMRT). This system involves a single-stranded molecule of DNA which attaches to a DNA polymerase enzyme. The DNA is sequenced as the DNA polymerase adds complementary fluorescently-labelled bases to the DNA strand. As each labelled base is added, the fluorescent colour of the base is recorded before the fluorescent label is cut off. The next base in the DNA chain can then be added and recorded.

SMRT is very efficient which means that fewer expensive chemicals have to be used. It is also incredibly sensitive, enabling scientists to effectively ‘eavesdrop’ on DNA polymerase and observe it making a strand of DNA.

The Single-Molecule Sequencing in Real Time (SMRT) developed by Pacific Biosciences.
Image credit: Genome Research Limited

SMRT can generate very long reads of sequence of 10-15 kilobases long.

SMRT can generate very long reads of sequence (10-15 kilobases long) from single molecules of DNA, very quickly.  Producing long reads is very important because it is easier to assemble genomes from longer fragments of DNA. It also means that for small genomes the complete sequence can be obtained without the need for the expensive and time-consuming gap closing methods that other technologies require. 

With third generation sequencing scientists can now begin to re-sequence genomes to achieve a higher level of accuracy.

With the introduction of such sensitive and cheap sequencing methods scientists can now begin to re-sequence genomes that have already been sequenced to achieve a higher level of accuracy. For example, using SMRT, Escherichia coli has now been sequenced to an accuracy of 99.9999 per cent!

Sequencing the human genome in this way won’t be possible for a while, but when it is, scientists predict that it will be possible to sequence an entire human genome in about an hour.

A mere decade on from the Human Genome Project and DNA is now being sequenced far quicker and more efficiently. 

Graph showing how the speed of DNA sequencing technologies has increased since the early techniques in the 1980s.

A graph showing how the speed of DNA sequencing technologies has increased since the early techniques in the 1980s.
Image credit: Genome Research Limited

This page was last updated on 2016-06-13