6 Genomics in Caenorhabditis elegans: So Many Genes, Such a Little Worm

Abstract

In 1965 sydney brenner selected Caenorhabditis elegans for his studies of development and the nervous system because of its simple anatomy, its stereotyped behavior, and the ease of genetic manipulation. Even at inception, the goal of studying the worm was an understanding of how genes dictated form and behavior. This holistic view of the organism (now dubbed “systems biology”) stimulated the collection of comprehensive data sets. The anatomy was described through serial electron microscopic reconstruction with the nervous system defined at the level of the synapse (White et al. 1986). The complete cell lineage of the 959 adult somatic cells was determined (Sulston and Horvitz 1977; Kimble and Hirsh 1979; Sulston et al. 1983) and found to be remarkably consistent animal to animal. Investigators commonly sought to collect all genes affecting a certain trait through mutations (however illusory that completeness might be in retrospect).

The construction of a clone-based physical map (Coulson et al. 1986Coulson et al. 1995; Sulston et al. 1988), one of the earliest genome projects, was undertaken in the early 1980s in the same spirit. The map of overlapping cosmids and later Yeast Artificial Chromosomes (YACs) (Coulson et al. 1988Coulson et al. 1991), along with efficient means of transformation, provided the community with the wherewithal to recover the DNA for any well-mapped mutant readily and rapidly. But perhaps more importantly, the existence of a nearly complete physical map in 1989 helped convince James D. Watson, head of the National Center for Human Genome Research at the time, that the worm should...