Zebrafish have become a popular organism for the study of vertebrate gene function1,2. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease3–5. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes6, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.

Caenorhabditis elegans (isolate N2 from Bristol, UK) is the first animal of which the complete genome sequence was available. We sampled genomic DNA of natural isolates of C. elegans from four different locations (Australia, Germany, California, and Wisconsin) and found single nucleotide polymorphisms (SNPs) by comparing with the Bristol strain. SNPs are under-represented in coding regions, and many were found to be third base silent codon mutations. We tested 19 additional natural isolates for the presence and distribution of SNPs originally found in one of the four strains. Most SNPs are present in isolates from around the globe and thus are older than the latest contact between these strains. An exception is formed by an isolate from an island (Hawaii) that contains many unique SNPs, absent in the tested isolates from the rest of the world. It has been noticed previously that conserved genes (as defined by homology to genes in Saccharomyces cerevisiae) cluster in the chromosome centers. We found that the SNP frequency outside these regions is 4.5 times higher, supporting the notion of a higher rate of evolution of genes on the chromosome arms.Caenorhabditis elegans is the first animal of which the genome was sequenced (The C. elegans Sequencing Consortium 1998). Recently, the genome sequence of Drosophila has also become available (Adams et al. 2000). C. elegans is a sexually-reproducing animal, but the egg-laying animals are actually hermaphrodites: They produce some sperm that they can use to selffertilize. Self-fertilization quickly results in inbred lines. Although the generation time of C. elegans is ∼3-4 days, it is likely that in the wild the average time of clonal expansion without male-female mating is much longer. The strain Bristol N2, of which the genome sequence was determined, was isolated from mushroom compost in Bristol, UK, before 1956(Nicholas et al. 1959Fatt and Dougherty 1963) and frozen by John Sulston in 1969 (Brenner 1974). This animal occurs worldwide; isolates have been found on all continents except Antarctica (Hodgkin and Doniach 1997). Based on restriction fragment length polymorphisms (RFLPs) associated with Tc1 transposons, at least 20 races were defined. Previous research has indicated that spontaneous mutation rates in C. elegans are low (Anderson 1995), except for transposon insertions in strains that show germ-line transposition. Most strains have been stored frozen since their isolation from nature (Hodgkin and Doniach 1997). For this reason we consider it likely that the single nucleotide polymorphism (SNP) pattern we observe in the strains is identical to that of the original isolate. In this paper we sampled the genome of different natural isolates of C. elegans for SNPs. We investigated the nature of the polymorphisms and determined how they are distributed over the chromosomes and whether we could see differences between coding and noncoding regions. We also investigated how SNPS are distributed over natural isolates from over the globe, and we used this to infer relati...

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