Tough Mining

Caenorhabditis elegans, a 1-mm soil-dwelling roundworm with 959 cells, may be the best-understood multicellular organism on the planet. As the most " pared-down'' animal that shares essential features of human biology—from embryogenesis to aging—C. elegans is a favorite subject for studying how genes control these processes. The way these genes work in worms helps scientists understand how diseases like cancer and Alzheimer's develop in humans when genes malfunction. With the publication of a draft genome sequence of C. elegans' first cousin, C. briggsae, Lincoln Stein and colleagues have greatly enhanced biologists' ability to mine C. elegans for biological gold. Every organism carries clues to its molecular operating system and evolutionary past embedded in the content and structure of its genome. To unearth these clues, scientists examine different regions of the genome, assembling data on sequences, genes, functional elements that are not genes (but that regulate them, for example), repeated sequences, and so on. By comparing the genomes of related organisms, researchers can see what parts of the genomes are conserved—highly conserved genes tend to be important—and then focus on these regions to track down genes and determine how they function. To construct a draft sequence of the C. briggsae genome, the researchers merged genomic data from three sources—one derived from whole-genome shotgun sequencing, another from physical genome mapping, and the third from regions of a previously " finished'' sequence. For the shotgun sequence, the researchers extracted DNA from worms, randomly cut it into short pieces, sequenced them, and then assembled overlapping sequences to create thousands of stretches of contiguous DNA sequence. To help fill in the gaps between these " contigs,'' Stein and colleagues developed a " fingerprint'' map of the genome as a guide for aligning the shorter fragments. The map also helped them identify inconsistencies and misalignments in the genome assembly. Finally, they integrated the previously finished sequence to improve the draft genome sequence. Using these massive datasets, the authors produced a high-quality genome sequence; although it does not quite meet the gold standard of a " finished'' sequence, it covers 98% of the genome and has an accuracy of 99.98%. After confirming the accuracy of the draft, the researchers turned to the substance of the genome. Examining two species side by side, scientists can quickly spot genes and flag interesting regions for further investigation. Analyzing the organization of the two genomes, Stein et al. not only found …