Genomics of Vertebrate Splicing Regulatory Elements

Gene Yeo1, Shawn Hoon2, Chris Burge, MIT;, IMCB, Singapore

We explore the distribution and conservation of vertebrate splicing regulatory elements given the availability of large-scale genomic data for Homo Sapiens, Mus musculus and Fugu rubripes. We present a simple method for studying the conservation and distribution of common regulatory elements. We observe that the classical splicing signals and a majority of the exonic splicing enhancers (ESEs) are conserved in vertebrates, and identify a common set of ESEs conserved in vertebrates. In addition, we identify a few intronic splicing enhancers (ISEs) that are not conserved between mammals and fish. This raises interesting questions about the evolution of splicing regulatory elements in vertebrate lineages. In addition, we explore the trans-factors that are known to bind these cis-regulatory elements, and observe that consistent with ESE-conservation, serine-arginine (SR) proteins are also strongly conserved across vertebrates. On the other hand, a subset of heterogeneous nuclear ribonucleoproteins (hnRNPs) which regulate splicing via intronic elements are not conserved between mammals and fish. These results demonstrate novel splicing differences in vertebrates, opening avenues to organism-specific techniques in gene-finding as well as experiments that explore organism-specific splicing elements.