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In celebration of the recent nobel prize awarded for the elucidation of ribosomes,I wanted to make this video about evolution, using the ribosome as an example.Here I will show how molecular interaction leads to enzymatic function and howCHANGES in molecular interaction leads to CHANGES in enzymatic function (Ribosomeis an enzyme, so this is relevant).This change in the function of enzymes is the essence of evolution. So first, Iwanted to use the example of the "How Ribosomes Work" video I made a while back.This video is really confusing if do not understand how ribosomes actually work.But the video uses state of the art tech. to simulate the action of ribosomalaccomodation of aminoacyl tRNA. They use an algorithm for the natural interactionof atoms. Everything works exactly as it does in real life and this shows us thatwe have a really good understanding of this process. Since all the algorithms andvariables were of natural means, we know that god is not involved pushing aroundeach ribosome.If you dont understand the basics of ribosomes, please watch VIDEO 1 below, whichshows you all the basics of aminoacyl tRNAs,r regular tRNA, mRNA, and how theyinteract.Then watch "How Ribosomes Work" (VIDEO 2 below)This also gives you an example of how evolution works. You see in Video2 there isa lot of molecular interaction going on. And THAT'S the theme of this video. Theaminoacyl tRNA( which I will abbreviate as tRNA for the rest of this example) hasto interact with the mRNA so that the correct codons match and hydrogen boding canoccur and then the tRNA has to navigate through the "gates" of the ribosome. Thetop of the tRNA has to navigate through the gates and the bottom has to bond withthe mRNA. In order to navigate through the gates the tRNA has to interact with theA-loop and the H89 sequences. It has to go through this corridor and go to thecenter of the ribosome.If the wrong tRNA with the wrong codon is attached to the mRNA, then there will bea weaker interaction between the mRNA and tRNA. This means that it will be muchharder for the tRNA to go through the corridor and get to the center of theribosome.Lets say that a random mutation causes the H89 to get bigger- in other words thecorridor gets smaller since H89 is one of the gates (think: bigger gate equalsnarrower corridor).The tRNA has to squeeze through this space with even more effort than before. Thismeans that it has to be even more tightly bound to the mRNA. This means that thewrong tRNA is not as likely to bind as the right tRNA. Therefore the resultingprotein will be more faithful to the mRNA than before (fewer wrong tRNAs equalmore accurate protein)Now lets say that a mutation makes the H89 smaller- in other words, the corridorgets wider. This means that the wrong tRNA can bind to mRNA and get through thatcorridor since less effort is required for the tRNA to get through. Since thewrong tRNA is much more likely to get through, the resulting protein will havemore mistakes.Do you see how molecular interaction leads to function? More importantly, do yousee how CHANGES in molecular interaction leads to CHANGES in function?
 
The molecular interaction of the aminoacyl tRNA with the gates changes thefunction of the ribosome, so that a bigger or smaller gate means a more or lessaccurate protein.So lets see how scientists use this idea in a practical method called SELEX (whichstands for Systematic Evolution of Ligands by EXponential enrichment). This isessentially evolution speeded up and takes advantage of molecular interaction.Lets say you want to produce an RNA molecule that binds to ATP- from scratch. (ATPis a molecule that is crucial to life, and here it is simply an example. Also,please follow the illustration in the description box). What you do is you startwith a column (a popular tool in chemistry) of resin with ATP attached. You send10 to the 15th power of random RNA sequences that are 25 nucleotides long throughthe column of resin. This high number of 10 to the 15th power ensures completerandomization of 25 nucleotides (since 4 to the 25th power is 10 to the 15th).Simply put, this is AS RANDOM as you can get.So what happens is that there are certain RNA sequences that will interact weaklywith the ATP and stick to them in the tube. Those that do not interact will flowright through the column and be washed away. Then you take those RNA moleculesthat bound to the ATP and run them through a cycle where you convert the RNA toDNA using reverse transcriptase and you convert the DNA back to RNA using RNApolymerase. All living things use RNA polymerase to convert DNA to RNA, so, thisis a completely natural process. The RNA polymerase adds new random mutations tothe RNA sequences. Then you run these new sequences with the new random mutationsthrough the column and repeat this cycle a dozen times until you end up with anRNA sequence that binds extremely tightly to ATP.So once again, interaction leads to function and CHANGES in those interaction (inthis case random mutations) leads to CHANGES in function (in this case tighterbinding to ATP). Using SELEX, scientists have isolated artificial ribosomes thatsynthesize artificial peptides (the word peptide simply means small protein). Whatis interesting is that these artificial ribosomes have highly conserved sequencesfound in all peptidyl transferase active sites same as in normal naturalribosomes. So artificially we came to the same conclusion as nature did, whichshows the importance of the idea of selection to evolution. Since the selection isthe same in both cases (which is that it needs to bind the amino acid to thegrowing peptide) we get the same result, even though we started with completerandom chance in the beginning. This is really important to understand: both thenatural and artificial means came to the same conclusion despite the random chancein the beginning, since the natural selection which was consistent in both cases.In the end the randomness is “forced” to converge on this sequence. This gives theillusion of “design”.So scientists have used a similar process to determine the complicated pathwaysthat require many cellular changes. For example, we have 20 amino acids commonlyused in our body. So how would nature add a new amino acid? How do we get from 19to 20 or 20 to 21. In order to do this we need three things: a new aminoacyl tRNAsynthase, a new tRNA with the proper codon and a new amino acid. The tRNA synthaseloads the proper amino acid into the tRNA. So it MUST be unique, along with thetRNA codon and the amino acid. Clearly, this is a complicated process, but byrunning many positive and negative selection cycles, they produced all the newcomponents required for this to work.There are two arguments that can be made against this: first is that this requiresa working RNA polymerase and a living creature to do all this. This argument isabout abiogenesis, so I will get to it in a later video. The second argument isthat since scientists were required for this experiment to work, it proves thatintelligence is necessary. Well consider what scientists did that was so profound
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