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 how
CHANGES in molecular interaction leads to CHANGES in enzymatic function (Ribosome
is an enzyme, so this is relevant).

This change in the function of enzymes is the essence of evolution. So first, I

wanted 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 ribosomal
accomodation of aminoacyl tRNA. They use an algorithm for the natural interaction
of atoms. Everything works exactly as it does in real life and this shows us that
we have a really good understanding of this process. Since all the algorithms and
variables were of natural means, we know that god is not involved pushing around
each ribosome.

If you dont understand the basics of ribosomes, please watch VIDEO 1 below, which
shows you all the basics of aminoacyl tRNAs,r regular tRNA, mRNA, and how they
interact.

Then watch "How Ribosomes Work" (VIDEO 2 below)

This also gives you an example of how evolution works. You see in Video2 there is
a lot of molecular interaction going on. And THAT'S the theme of this video. The
aminoacyl tRNA( which I will abbreviate as tRNA for the rest of this example) has
to interact with the mRNA so that the correct codons match and hydrogen boding can
occur and then the tRNA has to navigate through the "gates" of the ribosome. The
top of the tRNA has to navigate through the gates and the bottom has to bond with
the mRNA. In order to navigate through the gates the tRNA has to interact with the
A-loop and the H89 sequences. It has to go through this corridor and go to the
center of the ribosome.

If the wrong tRNA with the wrong codon is attached to the mRNA, then there will be
a weaker interaction between the mRNA and tRNA. This means that it will be much
harder for the tRNA to go through the corridor and get to the center of the
ribosome.

Lets say that a random mutation causes the H89 to get bigger- in other words the
corridor gets smaller since H89 is one of the gates (think: bigger gate equals
narrower corridor).

The tRNA has to squeeze through this space with even more effort than before. This
means that it has to be even more tightly bound to the mRNA. This means that the
wrong tRNA is not as likely to bind as the right tRNA. Therefore the resulting
protein will be more faithful to the mRNA than before (fewer wrong tRNAs equal
more accurate protein)

Now lets say that a mutation makes the H89 smaller- in other words, the corridor
gets wider. This means that the wrong tRNA can bind to mRNA and get through that
corridor since less effort is required for the tRNA to get through. Since the
wrong tRNA is much more likely to get through, the resulting protein will have
more mistakes.

Do you see how molecular interaction leads to function? More importantly, do you
see how CHANGES in molecular interaction leads to CHANGES in function?
The molecular interaction of the aminoacyl tRNA with the gates changes the
function of the ribosome, so that a bigger or smaller gate means a more or less
accurate protein.

So lets see how scientists use this idea in a practical method called SELEX (which
stands for Systematic Evolution of Ligands by EXponential enrichment). This is
essentially evolution speeded up and takes advantage of molecular interaction.
Lets say you want to produce an RNA molecule that binds to ATP- from scratch. (ATP
is 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 start
with a column (a popular tool in chemistry) of resin with ATP attached. You send
10 to the 15th power of random RNA sequences that are 25 nucleotides long through
the column of resin. This high number of 10 to the 15th power ensures complete
randomization 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 weakly
with the ATP and stick to them in the tube. Those that do not interact will flow
right through the column and be washed away. Then you take those RNA molecules
that bound to the ATP and run them through a cycle where you convert the RNA to
DNA using reverse transcriptase and you convert the DNA back to RNA using RNA
polymerase. All living things use RNA polymerase to convert DNA to RNA, so, this
is a completely natural process. The RNA polymerase adds new random mutations to
the RNA sequences. Then you run these new sequences with the new random mutations
through the column and repeat this cycle a dozen times until you end up with an
RNA sequence that binds extremely tightly to ATP.

So once again, interaction leads to function and CHANGES in those interaction (in
this case random mutations) leads to CHANGES in function (in this case tighter
binding to ATP). Using SELEX, scientists have isolated artificial ribosomes that
synthesize artificial peptides (the word peptide simply means small protein). What
is interesting is that these artificial ribosomes have highly conserved sequences
found in all peptidyl transferase active sites same as in normal natural
ribosomes. So artificially we came to the same conclusion as nature did, which
shows the importance of the idea of selection to evolution. Since the selection is
the same in both cases (which is that it needs to bind the amino acid to the
growing peptide) we get the same result, even though we started with complete
random chance in the beginning. This is really important to understand: both the
natural and artificial means came to the same conclusion despite the random chance
in 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 the
illusion of “design”.

So scientists have used a similar process to determine the complicated pathways

that require many cellular changes. For example, we have 20 amino acids commonly
used in our body. So how would nature add a new amino acid? How do we get from 19
to 20 or 20 to 21. In order to do this we need three things: a new aminoacyl tRNA
synthase, a new tRNA with the proper codon and a new amino acid. The tRNA synthase
loads the proper amino acid into the tRNA. So it MUST be unique, along with the
tRNA codon and the amino acid. Clearly, this is a complicated process, but by
running many positive and negative selection cycles, they produced all the new
components required for this to work.

There are two arguments that can be made against this: first is that this requires
a working RNA polymerase and a living creature to do all this. This argument is
about abiogenesis, so I will get to it in a later video. The second argument is
that since scientists were required for this experiment to work, it proves that
intelligence is necessary. Well consider what scientists did that was so profound
and unnatural. They ran RNA through a column in order to allow it to interact
with molecules inside that column. Everything else is natural: the reproduction,
the random mutations, random selection, etc.

All the scientists did was to run that RNA through that column. Well nature can do
this too through the process of diffusion, etc., but of course it takes a lot
longer for two molecules to float towards each other in nature than it does in the
lab. But that’s all, and that’s why evolution takes millions of years in nature
and only a day or two in the lab.