C. elegans Genome Project

Working notes, graphs, sequencing data, protocols, match data, and restriction digest gel pictures and autoradiographs relating to C. elegans genome mapping and sequencing, Includes details of cosmids, YACs (Yeast Artificial Chromosomes), cDNA, knockouts, and RNAi. Also includes extensive correspondence with other worm laborartories around the world.

1978-2002

104 files

Arranged chronologically unless there are clear series of records.

The mapping and sequencing of the reference genome for the nematode Caenorhabditis elegans(C. elegans) was a joint project between a team led by John Sulston and Alan Coulson at the Laboratory of Molecular Biology (LMB), and later the Sanger Centre, and Bob Waterston's team at The Genome Institute at Washington University, St. Louis. The C. elegans genome project was based on openness and collaborative to create a resource for the worm community. It was the first animal to have its genome sequenced. The genome, consisting of 100 megabases of DNA on six chromosomes (autosomes I-V and X), was published in a special edition of Science on 11 December 1998. The last remaining gap was closed in 2002.

When Fred Sanger retired from the LMB in 1983 his research officer Alan Coulson went to work with John Sulston on C. elegans. Sulston planned to map the genome of the nematode because at that time it was the only realistic option for large genomes. In the early 1980s the only thing that DNA could successfully be grown in was a bacterium which produced pieces about 40 kilobases long. Sulston and Coulson developed a fingerprinting technique to build a physical map of the genome based on these cosmid clones. Overlaps between these clones were recorded by Coulson as pencil lines in a notebook, which were subsequently rubbed out and redrawn when new information became known. By 1986 they had successfully managed to organise their 17,000 cosmids into 700 groups, but there were large fragments of DNA that would not grow in bacteria. Yeast artificial chromosomes (YACs) allowed larger fragments of DNA to grow in yeast cells and were used to bridge the gaps in the cosmid map so that by 1992 the physical map covered the majority of the genome with only 6 gaps remaining.

Through close cooperation with the wider worm community, the high-quality physical map was aligned with genetic maps. This combined map was shown at the 1989 worm meeting at Cold Spring Harbor Laboratory. Sequencing the genome was now the next obvious step and due to improvements in sequencing and biological computing was now possible. The success of the mapping project helped to persuade James Watson to fund a trial sequencing project for 3 megabases of the C. elegans genome during the early stages of the Human Genome Project.

In 1992 the Wellcome Trust and Medical Research Council agreed to fund a new research centre, the Sanger Centre, that would play a role in mapping, sequencing and decoding the human genome and the genomes of other organisms. The C. elegans genome project team at the LMB moved to the Sanger Centre in 1993.

More information about the use of C. elegans as a model organism can be found in In the beginning was the worm: finding the secrets of life in a tiny hermaphrodite, Andrew Brown (Simon & Schuster, 2003).

A digitised copy is held by Wellcome Collection as part of Codebreakers: Makers of Modern Genetics