I recently had a chance to talk science with my old friend and colleague Jack Greenblatt. He has recently teamed up with some of my other colleagues at the University of Toronto to publish a paper on alternative splicing in mouse cells. Over the years I have had numerous discussions with these colleagues since they are proponents of massive alternative splicing in mammals. I think most splice variants are due to splicing errors.
There's always a problem with terminology whenever we get involved in this debate. My position is that it's easy to detect splice variants but they should be called "splice variants" until it has been firmly established that the variants have a biological function. This is not a distinction that's acceptable to proponents of massive alternative splicing. They use the term "alternative splicing" to refer to any set of processing variants regardless of whether they are splicing errors or real examples of regulation. This sometimes makes it difficult to have a discussion.In fact, most of my colleagues seem reluctant to admit that some splice variants could be due to meaningless errors in splicing. Thus, they can't be pinned down when I ask them what percentage of variants are genuine examples of alternative splicing and what percentage are splicing mistakes. I usually ask them to pick out a specific gene, show me all the splice variants that have been detected, and explain which ones are functional and which ones aren't. I have a standing challenge to do this with any one of three sets of genes [A Challenge to Fans of Alternative Splicing].
- Human genes for the enzymes of glycolysis
- Human genes for the subunits of RNA polymerase with an emphasis on the large conserved subunits
- Human genes for ribosomal proteins