okay chapter 25 bio 107 human biology this chapter we're going to talk a little bit about the structure of dna how it gets replicated and then how genes can be read to actually make proteins and then the things that the cell does need so overall the structure of dna was discovered in 1953 they did this by taking x-rays of of the dna and then they were able to determine that it was a series of nucleotides and then each one of those nucleotides has three parts or subunits first there's a phosphate there's a sugar and then there's a nitrogen containing base and it's these three parts that are going to make up each one of the nucleotides so dna we only have four bases we only really have four nucleotides to form all of the dna and decode for all of life on this planet there are two purines now purines are named for their chemical structure but essentially they have two rings to them so this is adenine this is guanine now the pyrimidines are made up of one ring chemically and i'll show you that in a little bit another slide so again all of the coding for life these four bases in dna and those pyrimidines are thiamin and cytosine so dna is a polynucleotide remember poly means many it is a very long strand in fact some strands of dna if you could stretch them out very so carefully they're going to be over six feet long in the human genome and again this is an alternating phosphate sugar backbone and that backbone is going to give the overall structure of the dna those nucleotides are actually going to be the coding portion of the dna so dna is a double helix it has two strands that are complementary to each other and what that means is both strand has exactly the same coding information to them the nucleotides always pair together adenine always pairs with thymine guanine always pairs with cytosine there are no known exceptions to that this always happens and this happens for our dna all the way down to the bacteria we don't see any examples that are different than this those two strands are called anti-parallel that means one runs forward the other one runs backwards but again they do code for the same thing the sugars are orientated a little bit differently and there's what's called a five prime and a three prime end on each end of dna just indicating that again this is an anti-parallel direction but each one of those strands does code for exactly the same thing here is that structure we start with our double helix this is probably recognizable to most of you even if you had in biology for a while this is a nice standard way to indicate dna structure as mentioned before there's a five prime in there's a three prime in and then we have our sugar phosphate backbone and then our nucleotides in the center remember a it's always going to pair with t g is always going to pair with c so again those pyrimidine is our single ring and then the purines are going to be double rings and then these are all held together by hydrogen bonding that keeps the two ends the two opposing strands together and that chemical orientation gives us this nice helical structure now to get the information off dna we actually have to make a copy of that but before we do that especially when a cell divides we need to replicate the dna and so first we need an enzyme dna polymerase this is the major enzyme that's going to help with dna replication dna polymerase is going to come in between the two strands open it up and it's going to allow for the replication of two identical dna strands this is what's known as a semi-conservative replication we're going to take one strand of the dna this is the original strand and we're going to use that as a template to produce a complementary strand that has again exactly the same information so that when we do fully replicate dna we get two new dna molecules with exactly the same information so again semi-conservative replication each daughter dna molecule consists of one new change of nucleotides and then one from the parent and the result are two daughter dna molecules again gender is not implied but just that we've come down like one generation we've actually separated the original dna molecule we have two daughter dna molecules but again those are identical that's important so we can conserve the information on these dna strands so again replication of dna we're going to break it down into different parts before replication begins and this is the most of the way the dna is going to spend most of its life the two strands are bonded together and this is a hydrogen bonding between the two nucleotides when it's time another enzyme called dna helicase it's going to unwind and unzip or break those bonds between the strands and then we're going to get two separate strands we're going to separate them a little bit as soon as we separate them in step three the complementary nucleotides are going to fit into the openings opened up by when we opened up these strands and again a with t c with g this is going to happen right there in that nucleus so once replication's taken down was is finished another enzyme called dna ligase is actually going to reseal each daughter strand together any breaks or any mistakes can also be repaired by dna ligase it's kind of like a spell checker to make sure that the dna has been copied correctly and then the results that five are two double helix molecules and these again have to be identical to each other from the original or the parental dna so let's look at this graphic kind of going over the replication so before replication we have the two strands remember there's a three prime there's a five prime they run in opposite directions but still they have exactly the same information on them c with g t with a and this doesn't change again this is conserved through all life as we know it now dna polymerase is the enzyme primarily responsible for the separation of the two strands and then once those strands are separated far enough the complementary nucleotides are going to come in and so this exposed t is now going to take up an a this exposed c is going to take up a g as we fill up these pairings we're going to exit the dna polymerase we're going to use dna ligase to help seal these up and then what we get on the other end of this are two identical daughter dna strands so again we start with the parental strand dna polymerase is going to separate it as we open up those base pairs the complementary nucleotides are going to fill those spaces and then dna ligase is going to make sure everything's sealed up and ready to go and then we end up with two daughter identical strands now the whole point of dna is to be able to code for life and code in the dna is broken down into little chunks called genes and gene is a coding sequence to synthesize a protein and there are literally thousands and tens of thousands of different proteins on each dna strand so gene expression is the process of using that dna to express the directions to make or synthesize a protein molecule this is going to involve three different types of rna we have messenger rna transfer rna ribosomal rna each one of these is going to have a role in copying the information and then eventual the protein synthesis so dna and rna do exist in every cell and so there is some subtle differences both have a sugar but in dna it's deoxyribose in rna it's ribose bases dna are adenine guanine thymine cytosine it's exactly the same thing in rna except uracil is going to replace thymine so that's the only difference there on the basis structurally dna is a double stranded where rna is a single strand and because of those two strands dna will form that helix when rna does not it just is a single strand in the cell so gene expression or getting the information from the dna to eventually make that protein involves two major processes transcription now transcription is literally the copying of the information on the gene from the dna the dna can't escape the nucleus and so we need to make a copy of mrna with the coding information so we can take that out into the cell that's going to take place in the nucleus so transcription happens in the nucleus now translation just like you're trying to translate two different languages this is going to take the coding in the mrna and then translate it into something useful like a protein this takes place in the cytoplasm this is used by reading the sequence of mrna bases that was made inside of the nucleus and then trna is going to help bring the amino acids to the ribosome rr rna so we have three types of rna we have the messenger rna we have the trna and then we have the r rna are all involved with that translation so again transcription this happens in the nucleus this is where a gene or a small portion of dna serves as a template to produce a complementary rna molecule so we want to kind of just copy the information on the rna produce an mrna so we can take that information out of the nucleus now definitions vary we have a historical definition where a gene was a nucleotide acid that coded for sequences of amino acids in a protein kind of a more modern equivalent of that is a gene is a genomic sequence directly encoding functional products either rna or protein so basically the same thing and the whole idea here is that a gene on a segment of dna is a coding region or a set of instructions to make something for the cell like a protein so our first rna our mrna messenger rna this is going to be produced again in the nucleus and this is going to carry genetic information from dna out of the nucleus to the ribosomes which are located in the cytoplasm so we can actually make our proteins again mrna is formed by the process of transcription or copying the information off dna remember this process is going to begin when a another enzyme called rrna polymerase is going to bind to what's called a promoter region in dna so this is like the start region for that gene it's the start of coding for that gene the dna helix is opened up so complementary base pairing can occur similar to what we saw just when we were making a new dna strand but remember when we make rna we're going to substitute that t for you uracil in the rna so as the copying progresses the rna polymerase is going to join new rna nucleotides in a sequence that is complementary to that of the dna what's meant to that is exactly the same information so that when we do get into the cytoplasm we can make that protein that was coded for from the dna and so when messenger rna forms it has a sequence of bases complementary to the dna but remember there is that one caveat we're going to take the a and substitute it for u any time we make mrna so again it's a t g c in dna but when we're making rna of any type it's always going to be u a c g so we start off with our double helix this is our strand of dna up here rna polymerase is going to come in here it's going to help unzip this particular sequence of dna and then as we progress forward from the promoter region we're going to separate the two strands this opens up our template strand and then the complementary bases from rna are going to join here and then remember any place where we would have had a t we're going to use a u for that so we're always going to substitute a u in rna when we're building from dna so this again is going to start in a region that's coded for the start of the gene it's going to progress until we get to what's called a terminator region or essentially the end of the information for that particular gene once that happens the dna strand is going to go back together the rna strand is going to be released and then we have a copy for that particular gene from the sequence of dna now before messenger rna is released into the cytoplasm it has to be processed a little bit and so the original copy off the dna strand is what's known as a primary mrna but it actually contains too much information because in the dna and then copied onto the rna we have regions called introns and exons now introns are sections of dna that aren't currently being used by the organism to code for anything and so they need to be edited out now exons this is the portion of the gene that we want this is the information to build that particular protein so we want to get rid of the introns we want to get rid of and conserve those exons so we have a complete blueprint once that happens there's a couple caps added there's a guanine cap that's added to one end and then what's called a poly a tail is added to the other end these are going to serve as protection for that mrna as it moves into the cytoplasm and then after we edit it the mature mrna is ready to leave the nucleus go to the cytoplasm so here's a section of that dna that we're going to transcribe we have the e's for exons we have the eyes for introns we're going to transcribe initially the entire section and take all of that information and so that's what happens in our initial transcription and remember transcription is just the copying of that information so this is what's known as our primary rna we need to then edit it so all of those introns are clipped out and then the exons are all fused back together on one end we have that poly a tail on the other end we have a cap and again these ends are served to not only protect the mrna as it moves through the cytoplasm but also it's going to be a single signal to the ribosome to which end it needs to read first so translation this is our second process this is where we're going to take the information in the mrna that nuclear information and we're going to be able to transfer it or translate it into a protein something the cell can use translation is going to require several steps using enzymes and different types of rna molecules again the three types that we've already mentioned mrna trna and then r rna something called the genetic code genetic code is broken down in a gene into three nucleotide units these are known as codons and so each codon or each unit that's going to be red again has three nucleotides to it there are 64 possible different codons now 61 of these are going to code for a particular amino acid that's going to help build our proteins the genetic code is said to be redundant in that some amino acids have numerous codewords or codons this is going to provide some protection against mutation or changes in the information being put into that protein now the three others of this 61 to make up 64. these are stop codons this is going to signal that we're done making our protein and we need to stop adding those amino acids we have a finished protein at this part now the genetic code again just like dna is universal in all living organisms like again meaning that the same codons for those same amino acids are going to code for structures in bacteria earthworms and then our cells now here is a very extensive table of all the different codons that we can possibly have and their amino acids that they they code for and so we know that a codon has three so the first base is on this column the second base is across the top the third pace is down the edge and so if we have a codon that has three u's we would first identify this we would go to the second base identify this column and then we'll go to third base and we would identify this particular amino acid if it's all c's we'd do the same thing we would go here we'd go to this column we would go up here and then we see that those three c's in our codon would be for proline a very specific amino acid but also in this column all of these particular different codons again a codon are the three letters they code for exactly the same amino acid and so this is the redundancy that's broken in and again this is to help prevent a lot of mutations going forward as mentioned before there are three stop codons these are them and this would occur at the end of a genetic sequence that codes for any protein and then always at the beginning of any mrna strand is a start or a promoter amino acid it's always going to be a u g now transfer rna is important because it's going to take the amino acids found in the cytoplasm back to the ribosomes so we can build our proteins they have kind of like a t shape or a bootleg shape due to how they come together those transfer or trnas are going to bind an amino acid at one end and then at the opposite end they have what's called an anticodon and this anticodon is going to be complementary to the codon on the messenger rna so it's going to match up if it doesn't match up it's not going to bring that amino acid and so it is the order of the mrna codons that determines the order in which the transfer rna brings in amino acids and then ultimately the order of those amino acids and our protein so this is our transfer rna on one end we have that anti codon that's going to match up with the mrna strand and then this transfer rna is specific for its amino acid arginine is going to be the one it will bring in if this anticodon matches up so again gene expression we have our dna double helix now we need to take the information in one of those strands and again it doesn't matter which strand because remember each strand codes for exactly the same thing this is transcription remember transcription is just the copying of the information once we do that we get our m rna which is broken down into codons and codons remember have three amino acid bases per codon translation the anticodon has to match up with the codon so we can see this that we know that c always pairs with g g always with c and then g always with c so that's the anticodon it's going to be the opposite of what's coming in to the ribosome and then we get our specific polypeptide or amino acid to match up with these codons and then remember every time we want to pair up enable the t if we're making mrna it's always going to be substituted with that u now ribosomes are r rna these as you know from our talk about the cells can be attached to rough endoplasmic reticulum or they can float free in the cytoplasm they are made up of two primary ribosomal subunits and these are just described as small and large just based on their their makeup and then right before translation they're going to join to form the ribosome now once formed it has a binding site for the m rna and then three sites for the trnas that are going to bring in those amino acid the binding sites are going to facilitate complementary base pairing between the trna anticodons and the mrna codons and also they're going to bring in the amino acids in line in a very specific order to form that polypeptide or that protein now after the mrna has attached to the ribosome the ribosome is then going to move down the length of the mrna reading the information now once it moves down a little bit further it is possible that other ribosomes may come in attached to the mrna at the start portion and then also start reading this way many proteins can be copied from the same strand and so we can just continuously go over and over using this same mrna to make multiple proteins if it's necessary so here's a cartoon of ribosome and the start of synthesis we have that small subunit we have the large subunit they're going to come together just before replication or production and then this mrna is going to come in and go through between these two subunits in this ribosome we have the trna binding sites and this ribosome then is going to travel the length of this mrna and as it does we're going to build proteins and remember we can have multiple ribosomes coming up and doing the same thing just kind of going along this coding information building the same protein this is actually a transmission micrograph of just that where you can see the ribosome you can see the strand the individual strands of the rna and these again are just going to follow each other and build the same protein so during translation codons remember codons have those three bases they're going to pair with the anticodons and they're going to be carrying specific amino acids that match up to the information on the codon again the order of the codons is going to determine the order of the trna entering the ribosomes and thus the sequence of amino acids that's being built on our poly peptide and again for that polypeptide for that protein to be functional we have to do this in order we can't jump forward all the information has to be in order so translation is going to involve three steps initiation this is an energy requiring step to bring everything together elongation elongation is the continued reading of the mrna building our polypeptide and then finally termination happens at that stop codon so initiation we're going to bring all of the translation components together we're going to assemble the ribosome we're going to bring in the mrna we're going to bring in our trna and then we're going to put it all together the initial or the initiator trna is going to attach to the start codon which if you remember is always going to be a u g and this is just a signal says hey start here so we can start building these polypeptide or this protein the ribosome again has three binding sites for trna it has a p site or a peptide site it has an a or an amino acid site and then it has an e or an exit site so first the small representative subunit is going to bind to our strand of mrna and then initiate your tnra is going to pair with the mrna and again the star codon is always aug after that happens the large ribosomal subunit is going to complete the ribosome so now it is completely functional the initiator trna is going to occupy the p site is now ready to accept the next trna which is going to come in again right off of that next codon now elongation is going to occur as long as we have mrna to be read and so this is the process in which we're going to build the polypeptide it's going to occur one of these amino acids at a time remember everything has to be in order and in addition to the trna the proteins called elongation factors are also required and what they do is they help facilitate the binding of the trna anticodons to the mrna codons of the ribosome again just making sure that everything is correct elongation can be broken down into two four steps first a trna was attached peptide is at the p site and then a trna carrying the next amino acid is arriving at the a site which is right next to it so once the next tna is in place at the a site the peptide chain will be transferred to this trna now energy is required so energy and part of the ribosome sodium you need to be bring about this transfer the energy contributes to the peptide bond formation which makes the peptide one amino acid longer by adding it to from the a site next we have translocation the mrna moves forward one codon length and the peptide bearing trna is now at the ribosomal sub rp site the spent trna exits back into the cytoplasm and then the new codon is at the a site and ready to receive the next complementary trna so again first a trna amino acid approaches the ribosome and binds at the a site remember we already have one here two rnas can be at the ribosome at the same time so the anticodons are paired to the codons peptide bond formation attaches the peptide chain to the newly arrived amino acid so we're going to take the peptide chain that was here and we're going to add it to the new amino acid that's just come in once that happens we're going to move over to the p site and then where the chain was the e site we're going to exit that trna back to the cytoplasm this opens up this site so we can have the next amino acid so we can keep building our polypeptide termination termination is the final step the new polypeptide and the components that carried out protein synthesis literally fall apart they all separate from one each other termination of polypeptide synthesis occurs at a stop codon remember there were three on that table and then termination requires a release factor protein in which cleaves the polyteptide from the last transfer rna ribosome then falls back apart back into a small and large subunit so upon termination the ribosome comes up to a stop codon on the mrna in this case we're looking at a u g a and then a release factor is going to bind to the side and then literally everything falls apart we have our polynucleotide we have our empty trna our large subunit our mrna and our small subunit so let's go through that process one more time the whole thing so dna first in the nucleus is going to serve as a template for mrna we have to do that because this dna molecule is simply too big to exit the nucleus so we need a messenger we need that mrna mrna remember is going to have the introns and the exons together so we have to edit it before it leaves so we have all exons when we take this dna out or this rna out of the the nucleus it's going to have a cap and a tail that's these yellow portions here and that's going to help protect it and guide it as we go through step three mrna is going to move into the cytoplasm it's going to connect up with the ribosomes once that happens the trnas with the anticodons carry out amino acids to the mrna the anticodon codon complementary base pairing occurs we build our polypeptides and then once we hit that stop codon again everything is going to disassociate we have a fully functional protein and then everything can be recycled at that point to build another protein now errors do occur and these are called point mutations and these are going to involve a single dna nucleotide when it gets copied now this is a very small part of the dna and actually a very small part of the mrna but it can have some circumstances that might cause issues first it might cause a change in a specific amino acid remember amino acid is coded by that codon those three letters that are in sequence or it may not have an effect at all it might produce an abno abnormal protein for example sickle so i'm going to back up i had a pause on this so first mutations can happen possible outcomes on that may cause a change in a specific amino acid so we might get another protein depending on where the mutation is it might actually have no effect we could produce a protein that's abnormal or could be dangerous to the humans or any organism this could be sickle cell sickle cell is a mis-shaped red blood cell and this can cause problems in some people that have this or it might produce an incomplete protein if we have that that protein is not functional so here's an example of where we had copying that works exactly as it should so we're going to have this dna strand we've gone through all the steps and then we get this polypeptide our protein this is where we are going to get a normal protein there has been a mutation but it occurs at a point where it still codes for the same amino acid here's an example of a substitution that took place this time we're going to get a substitution in the amino acid this is going to make a different protein and again this might be beneficial it could be dangerous or we could have something called a deletion where we've actually deleted an entire codon or an entire amino acid when we copied it and we get an incomplete protein this one has actually stopped too short so this protein will not be functional this is an example of sickle cell this is a normal red blood cell it's a nice flat cell it's got a couple dimples on each side but a simple said real blood cell has a mutation in its proteins that make up its structure and this cell will take on a mishap and shape the cell flows nicely through the cardiovascular system this one with its jagged edges may clump and cause blockages so frame shift mutations one or more of the nucleotides are either inserted or deleted from dna and so the result can be a completely new sequence of codons and a non-functional protein so here's an example of five codons that make up this sentence the cat ate the wrap now when we copy if we've actually deleted one of these sequences we have something called a frame shift where the c is gone and so now all of these letters are going to be shifted over and so the first codon is the same but now the second the third the fourth are completely different and then the fifth is incomplete so we're not going to get a complete protein from this so this is a frame shift where we've actually added something or in this case we've actually deleted some information now some mutations are the root of cancer in fact most cancers are caused by mutations in the cell replication process most cancers very greatly in fact there are hundreds of different types of cancers but most cancers begin as an abnormal cell growth that is something called benign this means that it will form a tumor but it's not going to spread so it's not determined to be cancerous and usually does not grow any larger its control now if growth continues that same original mutation might cause a tumor that becomes malignant that means it's cancerous and it possesses the ability to spread through the rest of the body by breaking off cells from the original tumors so benign growth is usually okay as long as it doesn't get too big but the malignant ones have the potential to spread through the body and start new cancers so here's an example this is what's called epithelial cells we'll be covering epithelia in different tissues in the next chapter but the epithelial cells are always on a surface so this could be your skin it could be the lining of any hollow organ in your body and so epithelia one of its characteristics is it has to be constantly replace and anytime you constantly replace a cell you lead to a point where you might get a mutation it's kind of like wearing out the machinery eventually something's going to go wrong and so if you have single mutation it's probably not a big deal but as this tissue gets older and if we add new mutations you might get a cell that has the ability to turn cancerous and if it does it might be able to spread if we keep mutating we get something that can grow into a larger tumor and this tumor now as it's beginning to have more and more cells eventually might be able to invade the underlying tissues and when it does that if it comes too close to a blood vessel or blood supply or too close to lymphatic vessels for fluid and part of your immune system it can actually travel these cells could actually travel to other parts of your body and so as that tumor grows it begins to go into the lower layers of the skin or surface and then again if it does go into these vessels these cells now have the ability to break off and then travel through these vessels and if that happens they can lodge in different parts of the body and so this is how cancer spreads it needs to travel again usually through the bloodstream or through the lymphatic system that is chapter