One of these days I'm going to get around to blogging about alternative splicing. As most of you know, the databases are full of information about alternatively spliced gene products in mammalian genomes. There are many scientists who believe that most mammalian genes have two or more different products as a result of alternative splicing of the primary transcript.
I think it's nonsense. When I look at my favorite genes, the HSP70 gene family, the predicted protein products make no sense whatsoever. (The image shows predicted splice variants of the HSPA5 (BiP) gene from the SpliceInfo database.) The alternatively spliced variant often removes a piece of the hydrophobic core of the protein or other parts that are known to be essential. Since these proteins are the most highly conserved proteins in all of biology, it makes no sense at all to predict that mammals have all of a sudden evolved variants that are missing large hunks of highly conserved amino acid sequence. I think that most predicted splice variants are artifacts of the EST databases.
The annotators of the human genome have pretty much rejected all of the splice variants of HSP70 genes (e.g., Entrez Gene HSPA5) and many other genes whose structures are known. They have not rejected the multiple splice variants of other genes that are less well studied.
Anyway, like I said, this discussion will have to wait for another time. Meanwhile, you can read my friend Deanne Taylor's views on alternative splicing (and her disagreement with me) on her blog [Alternative Culture]. She will be here in Toronto next summer to debate the issue so everyone should plan on attending a mini-Howlerfest. It will be at the same time as the Darwin Exhibit at the ROM [Charles Darwin Is Coming to Toronto].
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