HGP history

Starting small

When the Human Genome Project was proposed, methods of sequencing DNA were costly and small scale. The fundamental method of 'reading' DNA using special bases called chain terminators, the use of very thin gel systems, the adaptation of efficient cloning methods and the method of 'whole-genome shotgun' were all developed by Fred Sanger and his group during the 1970s.

Sanger's group produced the first DNA whole genome sequence (for a virus called phiX174 that grows in bacteria) of just over 5000 base pairs. They went on to sequence the first human genome (that of the DNA in mitochondria - small energy factories in all our cells that have their own genome of about 16,000 base pairs).

The first genome to be sequenced by the Sanger method was in 1982, for a virus called phage lambda that grows in bacteria. To sequence this virus genome - about 48,000 base pairs - Fred developed a method called the whole-genome shotgun, where the the whole genome is chopped into tiny sections right at the beginning of the research.

The approach has been refined to tackle ever more complex genomes. In 1995 the genome of Haemophilus influenzae, the first genome of a free-living organism to be sequenced, was tackled using the whole genome shotgun. It took about 18 months to sequence the 1.8 million base pairs.

During the Human Genome Project, early work focused on establishing mapping and sequencing techniques, especially in 'model' organisms. These organisms are interesting and, as 'simpler' organisms, they tend to have relatively small genomes - some are only a 10th to 1000th of ours. During this phase, bacterial species were targeted, as well as the genome of yeast which was completed in 1996.

By 1998, researchers from the Sanger Centre in the UK and the Genome Sequencing Center at Washington University reported that they had sequenced the entire genome of a nematode worm, C. elegans. Although, if you compare their bodies, a worm may not seem to be enough like a human to be of any use. The DNA code of a worm works in a very similar way to the DNA of a human. The same techniques that were used to sequence the worm DNA could be used to sequence the human DNA. The main difference between worm DNA and human DNA lies in the amount; a human genome has about 30 times as much DNA as a worm genome.