PUFFERFISH GENOME SEQUENCE UNVEILED: SINGAPORE AT THE FOREFRONT OF GENOMICS

An international team of scientists based in Singapore, Cambridge UK and California today announced the publication in Science Magazine of their work describing the sequencing and preliminary analysis of the genome of the Japanese pufferfish, Fugu rubripes. This marks the first publicly funded sequencing of a vertebrate genome to be published after the human genome, and is an important milestone for groups using the genomes of backboned animals in the intensive effort to decode the human genome. The sequence and annotations have been made freely available to all, without restrictions.

The pufferfish genome was chosen over a decade ago, as a potential model vertebrate genome because of its compact size.

Some of the key findings in this work include:

(a) The team found that the number of genes in the pufferfish is approximately the same as in man. However, as many as a quarter of all human proteins could not be recognized in the pufferfish sequence when the two genomes were compared directly. It has been speculated that the human complexity must have arisen from differences in gene splicing or gene expression. Comparisons between the pufferfish and human show that evolution of the protein sequences themselves is a significant component of the differences between the two species. Direct comparisons between animals in this way help to define the most rapidly evolving human proteins for further study.

(b) Comparisons of the pufferfish sequence with human sequence allowed the team to predict the existence of human genes which so far have not been found with other methods. Using the pufferfish genes they found evidence for about 1000 human genes which had not been found in other databases.

(c) The work also revealed how the gene arrangement in the two genomes is shuffled over time. While shuffling of the order of genes along the chromosomes is known to occur, this study has revealed in detail for the first time the extent of this reordering.

(d) There were a number of unexpected findings reported by the group - for example, the presence of a relative handful of "giant" genes - genes which appear bigger than their human counterparts unlike the majority of compact Fugu genes.

(e) The approach used to obtain the sequence of the pufferfish was similar to that used by Celera in obtaining the human genome sequence. DNA fragments were sequenced at random and the order then assembled in a computer, without first making ordered segments or maps of the genome, the so called "whole genome shotgun"(WGS) method. There has been great controversy about the effectiveness of this method. This report shows that at least for this complex genome, the WGS approach can produce genome sequence suitable for analysis. The great advantage is speed and cost; the consortium took only a few months to obtain all the sequence.

The work described in the paper was the result of a major collaboration between the Institute of Molecular and Cell Biology (IMCB) in Singapore and the other members of the consortium which include the Joint Genome Institute, Department of Energy, USA; the UK Medical Research Council's Human Genome Mapping Resource Centre (HGMP-RC), the University of Cambridge, UK; and the Institute for Systems Biology in USA. The Consortium was formed in November 2000 to draft sequence, assemble and ultimately finish the Fugu genome and disseminate the information to the greater research community. It has also resulted in the creation of a powerful genome bioinformatics group within IMCB, whose work in leading the annotation and analysis of the Fugu sequence will continue into the future. The researchers are already using the Fugu sequence and that of other vertebrates to map the locations of gene regulatory elements in the human genome. Singapore’s co-leadership in this project has placed her at the forefront of international genomics and bioinformatics.

The team plans to fully sequence and analyse the Fugu genome by April 26th 2003, but in the interim will release sequence updates and improved sequence annotations on a regular basis through the project websites:

http://www.fugubase.org
http://www.jgi.doe.gov/fugu

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Press Contacts:

Samuel Aparicio +44 777 189 2667 (saa1000@cam.ac.uk)
Sydney Brenner +1 858 551 8802 (sbrenner@salk.edu)
Elia Stupka +65 6874 1467 (elia@fugu-sg.org)
Byrappa Venkatesh +65 6874 3383 (mcbbv@imcb.nus.edu.sg)