The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phytogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.
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An international initiative to sequence the genome of Dictyostelium discoideum AX4 (refs 5, 6) was launched in 1998. The high repeat content and (AþT)-richness of the genome (the latter rendering large-insert bacterial clones unstable) posed severe challenges for sequencing and assembly. The response to these challenges was to use a whole-chromosome shotgun (WCS) strategy, partially purifying each chromosome electrophoretically and treating it as a separate project. This approach was supported by novel statistical tools to recover chromosome specificity from the impure WCS libraries, and by highly detailed HAPPY maps that provided a framework for sequence assembly. These approaches have enabled the completion of this difficult genome to a high standard, and are likely to be valuable in tackling the many other genomes that present challenges of composition and complexity.
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