MOTIVATION: The gene concept has recently changed from the classical one protein notion into a much more diverse picture, where overlapping or fused transcripts, alternative transcription initiation, and genes within genes, add to the complexity generated by alternative splicing. Increased understanding of the mechanisms controlling pre-mRNA splicing is thus important for a wide range of aspects relating to gene expression. RESULTS: We have discovered a convex gene delineating pattern in the strength of 5' intron splice sites. When comparing the strengths of > 18,000 intron containing Human genes, we found that when analysing them separately according to the number of introns they contain, initial splice sites were always stronger on average than subsequent ones, and that a similar reversed trend exist towards the terminal gene part. The convex pattern is strongest for genes with up to 10 introns. Interestingly, when analysing the intron containing gene pool from mouse consisting of >15,000 genes, we found the convex pattern to be conserved despite > 75 million years of evolutionary divergence between the two organisms. We also analysed an interesting, novel class of chimeric genes which during spliceosome assembly are fused and in tandem are transcribed and spliced into a single mature mRNA sequence. In their splice site patterns, these genes individually seem to deviate from the convex pattern, offering a possible rationale behind their fusion into a single transcript.

SUMMARY: InterMap3D predicts co-evolving protein residues and plots them on the 3D protein structure. Starting with a single protein sequence, InterMap3D automatically finds a set of homologous sequences, generates an alignment and fetches the most similar 3D structure from the Protein Data Bank (PDB). It can also accept a user-generated alignment. Based on the alignment, co-evolving residues are then predicted using three different methods: Row and Column Weighing of Mutual Information, Mutual Information/Entropy and Dependency. Finally, InterMap3D generates high-quality images of the protein with the predicted co-evolving residues highlighted. AVAILABILITY: http://www.cbs.dtu.dk/services/InterMap3D/.