Happy accidents are pretty much the corner stone of science: take Fleming’s revolutionary discovery of penicillin. But as students I think the view we get of science is one of very rigorous planning, meticulous methods and knowing exactly what results should be – I think a lot of students feel a big sense of shame when labs don’t go exactly as planned.
At the moment a lot of my modules are based around genetics, DNA and proteins. Yesterday, in my DNA technology lecture, we discussed a paper (I’ll put the full reference at the bottom of this post) where they took 3 different genes for Cytochrome p450, an enzymatic catalyst involved in mono-oxygen reactions and mammalian xenobiotic metabolism, and transferred them into a plasmids. These plasmids were then broken down into very small fragments, and then a DNA ligase was introduced to combine these fragments into novel plasmids.
The thing that really struck me about this was the lack of control you could have over the products. The purpose of this process, known as gene shuffling, is that you may find a gene which produces a better protein – perhaps with better working pH or temperature, or special properties like acid-resistance. We term these chimeric genes, derived from the mythical animals which were made up of various animals. But if you look at the way the actually process works, a tiny, tiny proportion of plasmids which are created are going to make any sense whatsoever, much less to resemble the properties of the original protein. Most will be missing entire domains of the protein, or will have multiple repeats of one section, there’s even a tiny chance of getting the exact same parental plasmid again. But occasionally, the chimeric gene created not only performs the function of the protein, but shows these amazing properties. Some genes created using this technique are now used to produce enzymes used in biological washing powders and paper manufacturing to aid the process.
This is an incredible example of ‘throw it all at the wall and see what sticks’ in science. And often times these studies will require multiple repeats just to find a single functional protein, and I’m sure there’s countless examples where months of work resulted in no real result. But I suppose that’s the beauty of real, academic science – nobody knows until you do, and there’s a lot of error that comes in trial and error!
Paper: Rosic NN, Huang W, Johnston WA, DeVoss JJ, Gillam EM. Extending the diversity of cytochrome P450 enzymes by DNA family shuffling. Gene. 2007 Jun 15;395(1-2):40-8. doi: 10.1016/j.gene.2007.01.031. Epub 2007 Feb 20. PMID: 17400405.
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