What are the factors that maintain or corrupt genome structure? How does selective pressure relate to genome context? To address these questions, we have undertaken a comparative analysis between the C. elegans genome and the recently completed genome of the related species, C. briggsae. This analysis has enabled us to construct a genome-wide catalog of conserved syntenic blocks and rearrangements and study them in relationship to known features.

This system offers three distinct advantages for studying genome structure. First, these genomes are computationally tractable (C. elegans: ~19K genes, 100 MB; C. briggsae: ~25K genes, 107 MB). Routine analyses typically requiring large computational clusters can be completed with much more modest clusters or even simple desktop systems. Second, the extensive functional knowledge of C. elegans, contained in an analysis-friendly format at WormBase (www.wormbase.org), facilitates connection of in silico predictions to the underlying biology. Finally, mutants carrying genomic rearrangements can be isolated and maintained as viable strains. Thus, comparisons between C. elegans and C. briggsae presents an ideal system in which to study genome structure from both computational and experimental perspectives, as well as to evaluate the methodology of whole genome analysis.

We determined the overall similarity of genome structure between C. elegans and C. briggsae using three methods: a gene-based method evaluating the simple collinearity of ortholog pairs, and two nucleotide level similarity algorithms, WABA1 and BLASTZ2. These methods result in increasing levels of sensitivity, ranging from ~50% to a maximum of ~80% of the C. elegans genome contained in syntenic blocks. We will present data examining the strengths and weaknesses of each method. To more fully understand the nature of genomic rearrangements, we have characterized breaks in synteny in relation to chromosome distribution, recombination frequency, repeat density, and operons. Breakpoints are most likely to be local, intrachromosomal events, occurring more frequently on autosomes than the sex chromosome. Interchromosomal events occur more frequently between autosomes than between autosomes and the sex chromosome. Recombinationally rich regions of C. elegans chromosomes also reveal an increase in breakpoint frequency. Similarly, regions enriched with repeats also exhibit higher number of syntenic breaks. Finally, the extensive operons in C. elegans are rarely disrupted by syntenic breaks. From this detailed analysis of synteny, we are now using syntenic blocks, breakpoints, and orthologs to characterize the selective pressure across the genome.