We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus , a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.

Down-regulation of E-cadherin expression is a determinant of tumor cell invasiveness, an event frequently associated with epithelial-mesenchymal transitions. Here we show that the mouse E12/E47 basic helix-loop-helix transcription factor (the E2A gene product) acts as a repressor of E-cadherin expression and triggers epithelial-mesenchymal transitions. The mouse E47 factor was isolated in a one-hybrid system designed to isolate repressors of the mouse E-cadherin promoter. Epithelial cells ectopically expressing E47 adopt a fibroblastic phenotype and acquire tumorigenic and migratory/invasive properties, concomitant with the suppression of E-cadherin expression. Suppression of E-cadherin expression under stable or inducible expression of E47 in epithelial cells occurs at the transcriptional level and is dependent on the E-boxes of the E-cadherin promoter. Interestingly, analysis of endogenous E2A expression in murine and human cell lines illustrated its presence in E-cadherin-deficient, invasive carcinoma cells but its absence from epithelial cell lines. This expression pattern is consistent with that observed in early mouse embryos, where E2A mRNA is absent from epithelia but strongly expressed in the mesoderm. These results implicate E12/E47 as a repressor of E-cadherin expression during both development and tumor progression and indicate its involvement in the acquisition and/or maintenance of the mesenchymal phenotype.

Gene duplication has been a major mechanism for increasing genomic complexity and variation during evolution. The evolutionary history of duplicated genes has been poorly studied along the vertebrate lineage. Here, we attempt to study that history by analyzing the expression of two members of the Snail family, Snail and Slug , in representatives of the major vertebrate groups. We find a surprising degree of variability in a subset of the expression sites for both genes in different species. Although some of the changes can be explained by neofunctionalization or subfunctionalization, others imply reciprocal changes in the expression of the two genes and the reappearance of expression in sites lost earlier in evolution. Because these changes do not fit easily into current models, we need to invoke additional mechanisms acting on enhancer elements to distribute expression domains and functions of duplicated genes unequally during evolution.