Alternative splicing and protein function

We have developed a method that generates possible mRNA isoforms for human genes contained in the EDAS database, taking into account the effects of nonsense-mediated decay and translation initiation rules, and a procedure for offsetting the effects of uneven EST coverage. Then we computed the number of mRNA isoforms for genes from different functional categories. Genes encoding ribosomal proteins and genes in the category "Small GTPase-mediated signal transduction" tend to have fewer isoforms than the average, whereas the genes in the category "DNA replication and chromosome cycle" have more isoforms than the average. Genes encoding proteins involved in protein-protein interactions tend to be alternatively spliced more often than genes encoding non-interacting proteins, although there is no significant difference in the number of isoforms of alternatively spliced genes.Filtering for functional isoforms satisfying biological constraints and accountung for uneven EST coverage allowed us to describe differences in alternative splicing of genes from different functional categories. The observations seem to be consistent with expectations based on current biological knowledge: less isoforms for ribosomal and signal transduction proteins, and more alternative splicing of interacting and cell cycle proteins.The current estimates of the prevalence of alternative splicing in the human genome fall into the interval 35–60% [1-7], whereas the estimated number of human protein-coding genes has decreased from more than 100 thousand [8] through 30–35 thousand [3,9,10] to 20–25 thousand [11,12]. Thus alternative splicing emerges as a major mechanism of generating protein diversity. Continuing sequencing of ESTs, whose number currently approaches 4 million, uncovers rare, tissue- and stage-specific isoforms. On the other hand, a considerable number of ESTs seem to arise from experimental artifacts (genome contamination, unspliced transcripts, computational errors leading to mis-alig