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I understand the role of alternative splicing in generating protein diversity, but for enzymes specifically, is alternative splicing responsible for the diversity of it? My professor told me something similar to the 1941 “one gene one enzyme” theory, and he said that “Enzyme diversity is coded for in the DNA, each enzyme is coded for by a separate gene, and splicing doesn’t generate the diversity.” I am a little confused because I thought one exception to the one-gene-one-enzyme theory was the mechanisms of alternative splicing… (obviously DNA itself also creates diversity but I don’t get why alternative splicing is not responsible for it)

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    $\begingroup$ It would help to get the exact words of your professor. AS definitely affects protein function (many papers out there, here is one random example). It may not dramatically affect qualitative enzymatic behavior but it certainly can change function. $\endgroup$ Apr 1, 2022 at 23:01
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    $\begingroup$ Please define precisely your usage of the word “diversity” as it applies to enzymes, and explain why you think enzyme diversity (as you intend it) differs from protein diversity in general. At the moment this is quite unclear to me. $\endgroup$
    – David
    Apr 16, 2022 at 22:09

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The "One-Gene-One-Enzyme" theory is rather outdated now and many of these "One-Gene-X" terms to define how genes work can be inaccurate. For example, after many modifications to that term, biochemist and geneticist George Beadle and geneticist Edward Tatum came up with the term "One-Gene-One-Polypeptide", and even then there are caveats. One is that Alternative Splicing means that one gene may code for more than "One" polypeptide. And two, that genes do not always code for polypeptides, that is, they may code for RNA strands that work to regulate gene expression (regulatory RNA), in fact, genes that encode for proteins constitute only around 1.5% of the human genome! (Source for this passage: Campbell's Biology 12th edition)

Back to the main issue, I wouldn't say that alternative splicing creates a "diversity" in genetic products, I think it is better worded that alternative splicing allows a greater range of products to be formed.

I do not have a specific, well-detailed example of how different enzymes are formed from the same gene that comes to mind, but it is definitely possible that if you can form different proteins from the same gene by shuffling the exon sequences, it can be possible that the shifting of the domains or usage of different subunits of an enzymatic protein by splicing exons in different fashions can affect how it functions.

I did, however, find a publication on PubMed whose abstract states that there are isoforms (protein variants) of Base excision repair enzymes (though at the time of the publication, their function does not seem to be explored).

There is also an example given on Wikipedia on protein variants that uses AMPK as an example of an enzyme formed by alternative splicing of subunits, where some combinations of subunits are more ideal in their function according to where they are located, such as the liver having a different preferred/abundant form of AMPK than human skeletal muscle.

I hope this answer gives you a nice clarification, if anyone finds something inaccurate please feel free to criticize!

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There are a lot of different mechanisms by which the "one-gene-one-enzyme" theory doesn't work. Alternative splicing is definitely one of them, but there are other biological processes like post-translational changes that can affect enzyme function. Also, it is very important to take into account that there are many enzymes that work as functional complexes with multiple subunits in which every subunit might (or might not) be coded by a gene with a certain pattern of splicing.

In summary, alternative splicing does contribute to the diversity in enzymes.

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  • $\begingroup$ Welcome to Biology.SE. Answers should focus on the question and are much more likely to receive a favorable response if they include supporting references (primary literature is best). Without that support, your answer is indistinguishable from opinion and thus inappropriate for this site. This is a good example of how to format references. In addition, it is best to leave unclear questions unanswered. ——— Please take the tour and consult the help center pages for additional advice on How to Answer and How to Ask effectively on this site. $\endgroup$
    – tyersome
    Apr 25, 2022 at 18:16

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