We have generated and analyzed >50,000 shotgun clones from 1059 Fugu cosmid clones. All sequences have been minimally edited and searched against protein and DNA databases. These data are all displayed on a searchable, publicly available web site at http://fugu.hgmp.mrc.ac.uk/. With an average of 50 reads per cosmid, this is virtually nonredundant sequence skimming, covering 30%-50% of each clone. This essentially random data set covers nearly 25 Mb (>6%) of the Fugu genome and forms the basis of a series of whole genome analyses which address questions regarding gene density and distribution in the Fugu genome and the similarity between Fugu and mammalian genes. The Fugu genome, with eight times less DNA but a similar gene repertoire, is ideally suited to this type of study because most cosmids contain more than one identifiable gene. General features of the genome are also discussed. We have made some estimation of the syntenic relationship between mammals and Fugu and looked at the efficacy of ORF prediction from short, unedited Fugu genomic sequences. Comparative DNA sequence analyses are an essential tool in the functional interpretation of complex vertebrate genomes. This project highlights the utility of using the Fugu genome in this kind of study.Despite massive investment in genome mapping and DNA sequencing over the last 10 years, large-scale sequencing of vertebrate genomes has been initiated only very recently. This is partly because the initial emphasis has been on developing mapping, sequencing, and assembly technologies and partly because sequence-ready contigs of large regions of the human genome have not been available. Many valuable lessons have been learned-at no small expense-from the bacterial, yeast, and, in particular, the Caenorhabditis elegans projects. It is also clear, however, that mammalian genomes may present additional problems relating to the generation of cloned DNA from some regions, sequence assembly of highly repetitive DNA, and the large size of the genomes involved.To interpret much of the data, comparative sequencing of genomic regions from other vertebrates will be necessary. The identification of conserved sequences across species has always been a key technique in the identification of genes. In addition, sequence comparison in invertebrate projects has identified many genes by sequence similarity and in many cases has allowed speculation on function. Now that the resolution of genomes is approaching the single base pair, powerful analytical methods need to be used to define the many elements-both coding and noncoding-that are contained within the human genome.Despite the need for comparison, there is little investment in other vertebrate sequencing projects at this time. Small regions of conserved synteny within the mouse genome have been pinpointed for complete genomic sequencing, and this will provide an opportunity to compare not only precise orders of genes but also regions in and around the coding sequence itself. This should lead to the identification of other con...

Twenty-seven genes have been cloned and mapped in Fugu which have orthologues within the human chromosome 9q34 region. The genes are arranged into five cosmid and BAC contigs which physically map to two different Fugu chromosomes. Considering the gene content of these contigs, it is more probable that a translocation event took place early in the Fugu lineage to split the ancestral 9q34 region onto two chromosomes rather than the alternative hypothesis of a large-scale duplication of the region into two chromosomes with subsequent rapid and dramatic gene loss. There are considerable differences in gene order between the two species, which would appear to be the result of a series of complex chromosome inversions; thus suggesting that there have been no positional constraints on this particular gene set.

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