Video 2-3: What are genes?

0:03 In the next section, we'll look at the main um mechanism by which the last two molecules that were discussed in the videos, nucleic acids and proteins are connected. This was mentioned um in the video as well. Uh but just very briefly um because this will play a role in the um algorithmic task we're looking at. I'll I'll show you another video about this in detail in a moment. But first the kind of schematic one. Um I forgot to ask about whether people already know this. Maybe we can because we're a tiny group. Uh who has seen this central dogma of molecular biology story before?

0:44 Anyone has seen it? Anyone's not seen it? Seen not seen. Uh so it's the term was coined by um by Watson one of the two discoverers or people that scientists that discovered the double helix structure of DNA is uh for for a long time this has been um the term and uh it's it's stuck with people. Um the main the main way how uh cells make chemical compounds is that DNA encodes a recipe that is first copied into a messenger RNA which is then translated into a protein and many of the maybe it's fair to say most of the mo more interesting chemical reactions are modulated or done by proteins. So this is uh the the key component. Now here's a schematic sketch. the video will have this 3D animation that makes it a bit more um graspable how this looks like and what the scales are. Uh but I think it's also good to have this Wikipedia image where everything is shown in one one uh one picture. So you have uh a cell stylized here and then the nucleus which is much smaller. Uh it's not to scale. There's one strand of of DNA here. Uh maybe let me use the the pen where it's a bit better to see.

2:10 Uh so here um remember the DNA is is this double helix. So to read off some part you have to uh separate the two strands. Um that's what the RNA polymerase does but again the names um are not important for us. So uh you unwind the two strands you make a copy of a certain piece and we'll come back to how on earth this molecule knows where to start and stop. that produces a copy that is singlestranded. It's chemically a little different than DNA. It's RNA, but they're very very similar. And the copies for all intents and purposes of our understanding is just a a digital copy is exactly identical in the content. Then this somehow uh this is where the story gets more complicated depending on what kind of uh living being we look at. The simplest version as it is in bacteria and archa is that essentially this thing just uh gets gets further translated and some steps here are skipped or ukareotic cells like all animals and all plants and all fungi. Uh the story is more more tricky. We'll come back to that a little bit but we will ignore ignore much of the complications there. So the essentially the copy is still a bit modified.

3:28 there's some some pieces cut out. Once this is done, um this mRNA exits the nucleus and is then in one of the ribosomes translated into a protein.

3:42 And that mechanism uh is also interesting of its own right. Well, the for the sake of this um unit will mostly focus on this first step and in particular this question, how do these things know where to start? There's nobody directing this. This is all decentralized and just uh chemicals floating in water. How do they know where to start and stop? Uh but of course all steps in this process are are super interesting and highly complicated. Uh so I'm not going to say this is one is more important than the other. It's just for the specific problem we're looking at, we'll focus on this first stage. Um the video I'm going to show is uh the same makers as the one we looked at uh last time. It's a stylized animation. It's not supposed to be realistic that exactly this is how things look. That's um there's some videos where people try to make it that way. Accurate simulations of the molecular structures. They're cool to look at but impossible to understand. And so I decided against that. Uh instead this one cheats a little bit and makes things a bit more symbolic. Um, but it goes through all of these steps and is much shorter than the other one. Uh, so let's briefly go go there.

5:12 Here is a cell, the basic unit of all living tissue. In most human cells, there is a structure called the nucleus. The nucleus contains the genome.

5:23 In humans, the genome is split between 23 pairs of chromosomes. Each chromosome contains a long strand of DNA, tightly packaged around proteins called histones.

5:41 Within the DNA are sections called genes. These genes contain the instructions for making proteins. When a gene is switched on, an enzyme called RNA polymerase attaches to the start of the gene. It moves along the DNA, making a strand of messenger RNA out of free bases in the nucleus. The DNA code determines the order in which the free bases are added to the messenger RNA.

6:11 This process is called transcription. Before the messenger RNA can be used as a template for the production of proteins, it needs to be processed. This involves removing and adding sections of RNA.

6:35 The messenger RNA then moves out of the nucleus into the cytoplasm. Protein factories in the cytoplasm called ribosomes bind to the messenger RNA. The ribosome reads the code in the messenger RNA to produce a chain made up of amino acids. There are 20 different types of amino acid. Transfer RNA molecules carry the amino acids to the ribosome.

7:09 The messenger RNA is read three bases at a time. As each triplet is read, a transfer RNA delivers the corresponding amino acid. This is added to a growing chain of amino acids.

7:32 Once the last amino acid has been added, the chain folds into a complex 3D shape to form the protein. Okay. So, uh always fun to see the different styles as well of how to make videos. The much more calm British version. Uh a lot a lot in there. Especially this last step is also super interesting and we'll come back briefly to that. Uh remember these little uh these T-shapes uh the pluses with the three things sticking out at the top and one amino acid at the top. Uh these realize what is nothing but a real uh translation code uh the genetic code if you want um where we have as input the copy of the DNA. So with these four bases and a chemical a nitpick here is that DNA has a T thomine and uricil is what the equivalent in RNA but they are otherwise so similar. They're chemically not the same but they behave in the same way. So you can ignore the difference but it is a bit annoying because you always have to replace T's by U's depending on uh which molecule you're talking about. So that's why there's a U in all these uh codes. Um and then it's always exactly three of these amino acid uh of these um uh sorry about the uh the bases nucleic bases that form that encode for one protein.

9:22 Uh the proteins here are denoted by these uh letters. They also have full names and abbreviations. There's essentially these 20 proteins there. Now, if you count, there's more than 20 things around here. Well, first of all, there's some letters occurring several times. It's it's arranged so that you can read that say a u a you follow from au and then the the last one tells you okay this is whatever you pronounce this like isoline.

9:52 Um, but there's also some special ones here that are marked with stop. That's one way to uh represent this code. So, it translates from the four letters of of DNA or RNA to the 20 letters of amino acids or peptides. And uh if you think about Okay, I forgot to switch on the mic. So this part is silent. Oops. Um is that true? Do I have two mics now?

10:41 I think this is Let me double check. Yeah, this one should have used. Uh oh, that's going to be interesting. The sound in the encoding. Well, not not too much that I said is not on the slides. Uh it's a code to translate from bases to peptides. Uh another way to draw the same code is is in this table uh where here it's listed by amino acid or by some of these special ones. There's the the start and stop codeons or um special markers. uh codon is just three amino three uh bases taken together encoding for one amino acid or these special markers start of translation and end of translation. And you also note that some amino acids have several codons, others have just one. And you may wonder why that is. Well, for one, the code is uh a bit generous. we have only around 20 amino acids but we could code for 4 to the3 power. So uh 64 different ones right. So there will be some some are not used or some are kind of duplicate and uh the way this this happens in nature which is the cause and which is the result is unclear. Uh but if you plot say in in humans um how often in the proteins that you can uh sequence in a cell you find the different amino acids.

12:27 There seems to be a strong correlation with the number of codons that this amino acid has. So in a way nature uh almost optimized um the code in in an evolutionary sense like the code got optimized via evolution by selection so that the amino acids that are used most often have several codons that code for them which means that a mutation in the DNA that is rare but occasionally happens might not have any consequence. If you have a mutation that turns this codon into this one, you replace this C by an A. This the protein that comes out of that is still the same. And if you do that for a protein for an amino acid that's used a lot, there's more mutations that are not affecting the function. Whereas for the uh for the rare protein for the rare amino acids uh it's it's annoying if they if a mutation there causes a change in function, but you'd rather have that at a place where it affects few amino acids than at a place where it affects many.

13:40 So it's a a kind of cute thing that happens here. Another thing that as I mentioned there's no rule in biology without an exception. First of all, usually these are stop codons. You can see here UG is listed there. It normally signals to the ribosome stop translating and finish this protein that you've sequenced. But sometimes with some chemical site conditions, it actually encodes for a 21st amino acid that's not otherwise used. And yet in other examples, there's even a 22nd. And if you go in the general realm, there's even many more amino acids that could sometimes be part of proteins um if they're sequenced with different means. So just keep keep in mind um that there's always these exceptions. Uh I've shown you this central dogma of molecular biology. The vast majority of proteins are sequenced via this route. You have the gene encoding the sequence for the protein which is first translated to RNA and then the ribosomes turn it into protein with this uh genetic code. But there's other mechanisms. There's other ways to sequence or to um synthesize proteins in the cells that don't go via the ribosomes and where the final protein is not found in any gene, not directly.

15:14 Then epigenetics means all the things that happen that are not directly just in the sequence of DNA. You may wonder why your body has the same DNA or same genetic the same genome in every cell and still your cells do different things. Uh that's part of epigenetics. There's additional markers that can be added to the genome on top of the four letters that uh make the cell develop in different directions. Uh there's funny things when you uh go to bacteria and archa because they don't have a nucleus in their cells. So the genome is essentially floating around in the cell freely and there's things that happen where essentially a little gene is just floating into the bacterium and then it's part of the genome and is inher is is inherited to its its children uh but it wasn't part of the original genome and that way they can pass genes between living uh bacteria without having to to uh split in and two in between. So even the whole notion of species for bacteria and archa is very unclear uh because they don't reproduce sexually. So there's no natural there there's many things that blur uh at the boundaries. Uh it's also fun to know there's some viruses that essentially work by inserting their genetic information into your genome and it stays there. So, we can trace back large parts of our genome to some ancient viruses and we're they're just part of us now. Fun, fun, fun.

16:51 And there's other active molecules. Some genes code for RNA, not proteins. But, uh, we'll ignore all of that for most parts. Okay.