Gene+Expression

For a great place to start go to this link []

[|Our Molecular Selves], introduces the connection between genes and our persons, why we need to know how DNA works to make proteins. this youtube clip takes 3 minutes to explain some basic ideas.

DNA replication
This cell process produces two copies of the set of chromosomes when a cell divides to make two cells. Replication means copying.

When do you make an exact copy of a set of chromosomes? When the cell is dividing, during the process of Mitosis.

DNA is a double strand so first it has to unzip so the two sides are exposed. New nucleotides are able to match up with the old nucleotide bases. You should remember that the nucleotide bases match up in a complementary way, A with T and C with G. (The original DNA strands are kept as part of the two new strands, this is called a semi conservative process).

The DNA zips up again

If only it was all there was to it. We do have to know more detail about the process. As you can see from this simple diagram, there are some new words here already.

Visit this website for an excellent but complex animation of DNA replication. Take your time to read and identify each element in the animation. http://www.johnkyrk.com, go to the DNA structure link and then the replication link. It is way too complicated for our level of biology, but it is impressive!

[] is also quite informative, if you like reading. Think about what you read.

We have had to add in some control processes, enzymes that control the stages. and **DNA Polymerase** enzyme to break open the hydrogen bonds between the base pairs,and makes new base pairs bonds form.
 * Helicase** and G**yrase enzymes** to unzip and unwind the double helix strand of the DNA

One strand of the DNA,called the template strand, or the leading strand, builds up one base at a time, the other ,called the lagging strand or the coding strand, builds up in chunks with gaps that get filled in later. DNA Ligase enzyme joins the bases in the gaps.

A chemical whose name ends in ...ase is a member of the enzyme family.

This diagram shows one nucleotide, it is made of a phosphate group, a sugar and a base. Remember that many nucleotides make a nucleic acid .

In this picture the sugar is deoxyribose, so the nucleic acid is DNA. What if the sugar was ribose, what nucleic acid would it make then?

DNA has a top and a bottom, in a nucleotide the Deoxyribose sugar is numbered off around the Carbon atoms, one end of the DNA is the 3' (3 prime) end (named after the 3 Carbon on the deoxyribose sugar) and the other end is the 5' end (5 prime ) (named after the 5 Carbon on the deoxyribose sugar).

Notice in the next picture how the DNA strands run opposite, 5- 3 one way goes top of the page to bottom of the page, and 5 to 3 on the other strand goes bottom of the page to top. This is called anti-parallel.

The template strand builds bases in the order starting from the new 5' end and going towards the new 3' end. I remember this because 5 to 3 is a good time of the day at school - nearly finished!.

The template strand also gets called the sense strand and the leading strand, in a confusing kind of a way, it is the template strand that you have to match up when you read the protein code.

Once the sets of chromosomes have been replicated, the rest of the cell undergoes mitosis and divides to make two exact copies of the original cell.

One of the practical applications of this information ( how DNA replicates) is in the Polymerase Chain Reaction, which people use to make multiple copies of DNA for their own use, e.g in forensics, in gene therapy, in DNA profiling...

DNA coils up and wraps around histones and other proteins in an organised way to shape the DNA into the chromosomes we are familiar with. There is a great 3D animation which explains the shape well. https://www.dnalc.org/resources/3d/07-how-dna-is-packaged-basic.html

Protein Synthesis
So why are chromosomes essential to our understanding of cell processes and of evolution.

The other job that chromosomes have (apart from making copies of themselves) is to control the proteins the cell makes. Different cells need to make different proteins depending on their role in the body. The genes that are located along the chromosome carry the DNA code for the structure of the proteins. The trick is to get the code from the gene out to the place in the cell where the proteins are made.

The gene is always kept in the DNA of the chromosome. It is the master copy that needs to be kept secure. The code of the DNA is copied by a similar molecule called messenger RNA. The mRNA goes out of the nucleus through a hole (called a nuclear pore) in the nuclear membrane. Once in the cytoplasm it goes to a ribosome. The ribosome attaches to the 5' end of the mRNA and starts to read the code. The code needs to be changed from being in base letters into the amino acids that proteins are built out of. The part of the process that changes the code into amino acids is the transfer RNA with reads off the mRNA bases,and brings in the amino acids that the instructions code for.

RNA has to be different from DNA. RNA has a different sugar in its nucleotide,it has ribose sugar (so the name changes to RNA instead of DNA). RNA is a short length chain while DNA is a long chain.Why do you think this is? RNA Is a single strand,DNA is a double strand. How do you think being a double strand helps DNA be stable? One of the bases in RNA is different, in RNA Adenine, A, pairs with Uracil, U. There is no Thymine in RNA molecules. You need to be able to recognise a molecule of RNA compared to a molecule of DNA.

The code for making proteins is based on a triplet code. This means there are 3 bases involved in coding for the amino acid. Three is an important number. If we only used 2 bases, we could only get 8 different amino acids organised, write out the letter A,C, G and U in pairs and see how many combinations you get. e.g AA, AU,AC,AG.......... There are 20 different amino acids involved in making proteins. That means we need to have enough base combinations to get up to 20. 2 base combinations aren't enough. 3 base combinations will provide 64 possible combinations, AAA, AAU,AAG, AAC......This gives us an excess, and therefore some combinations code for the same amino acid. This actually becomes useful. Having an excessive amount is called redundancy.

So adding in some specific language now
Step One - copying the DNA into the mRNA is called Transcription. The three bases in the DNA are called triplets. The mRNA reads the template strand, matching complementary bases to the DNA base, except where there is an A it pairs with a U. (The mRNA actually ends up being identical to the coding strand of the DNA, except for T and U). Step Two- changing the bases into amino acids is called Translation. The 3 bases on the mRNA are called a codon. The tRNA reads the codon and makes a complementary base pair match. The 3 bases on a tRNA are called an anticodon. As the amino acid arrives at the ribosome in the right order, a peptide bond forms between the amino acids. The chain of amino acids is called a poly- peptide.

This is the end product of the process, a poly-peptide is part of a protein. One gene will code for one poly-peptide. If you need two poly-peptides, how many genes will you need to make them? The mRNA keeps on reading the gene in the DNA over and over again, until the protein doesn't need to be made. Some proteins need to be made forever, all the time. Others only some of the time.

Animation time! Check out these youtube clips, [|amoeba sisters is most straightforward,] Try the link to Amoeba sisters first, I love the last one but be warned, it has a little more detail than we need, but that won't hurt you. I will know when you have seen this clip - you are definitely going to want to tell me about it. Transcription to protein synthesis -[|RNA to protein synthesis]Protein synthesis version (bit boring) of an [|animated biology talk-]AND click here to go to my [|favourite version-], turn the speakers up first.

Revision
Make a list of keywords from the paragraphs above about protein synthesis. For each key word explain why it is important for you in understanding the steps in protein synthesis. You should get about 25 key words I reckon.

Make a mind map that links that steps, the locations of each step and the molecules involved.

Answer some past paper questions at the NZQA website (http://www.nzqa.govt.nz/qualifications-standards/qualifications/ncea/subjects/ ) Look up the answers to see what you needed to say to reach excellence.

Metabolic Pathways
The proteins the cells make in their ribosomes travel along the endoplasmic reticulum, are packaged up in the golgi bodies in the cytoplasm and sent off in vacuoles to work their job.

Some proteins are enzymes. Enzymes are catalysts, they speed up a chemical reaction. A series of chemical reactions that changes a reactant into a product the cell can use is called a Metabolic Pathway. These step pathways rely on a different enzyme for every step. (That means they rely on different genes to make those different protein enzymes eh).

Chemical 1 is processed into Chemical 2, is then processed into chemical 3

Step 1 needs enzyme 1 step 2 needs enzyme 2

gene 1 codes for enzyme 1 gene 2 codes for enzyme 2

If one step can't happen because the enzyme for it hasn't been made, the whole metabolic pathway after that enzyme step can't proceed. These errors often show up as a disorder. There are some classic studies about these metabolic pathways.

Did you know you were tested for the disorder Phenylketonurea when you were born (if you were born in NZ ).



This is a classic disorder caused by lack of an enzyme (there are several steps that can have an enzyme that can be missing). If you inherit a recessive allele so your cells do not make the normal enzyme your cells will not be able to process phenylalanine normally. We test all our babies because a special diet can manage the symptoms of this disorder. Meat,fish eggs,milk are all foods that are high in the amino acid phenylalanine. The sugar substitute aspartine also contains phenylalanine,so even diet soft drinks have it! The symptoms of PKU include a mousey body odour, mental retardation and dark urine.

There is no 'cure' as the recessive allele located on Chromosome 12 is present in every cell in the body,but appropriate lifestyle can manage the disorder. This family have two children who manage their diet. http://magazine.merckgroup.com/en/Life_and_Assistance/metabolic_disorder/PKU1.html?magazineRateArticle=tcm:1113-94781-64

The first enzyme that could be missing is called phenylalanine hydroxylase, which converts phenylalanine into tyrosine. The phenylalanine starts to buildup and poisons the cell, causing PKU disorder. Albinism is another disorder on this metabolic pathway. It is caused by lack of the enzyme that processes melanin, so sufferers have no dark pigment in their cells. Alkaptonurea is another disorder on this metabolic pathway, typified by dark urine. A fourth disorder on this pathway is Cretinism, where sufferers have severe mental retardation as a result of lack of enzymes required to process chemicals in the thyroid gland.

So each step has to have a functioning enzyme for further steps along the pathway to be able to work properly.

Inherited Metabolic Disorders. New Zealand woman, Samantha Lenik, has a disorder caused by lack of an enzyme. She needs to raise $500, 000 every year for treatment. The disorder is called Pompe disease and is caused by a build-up of glycogen in the body’s cells, which over time causes the muscles, in particular the legs and diaphragm, to weaken. It will cause breathing problems that will lead to respiratory failure. More information is available at https://nz.lifestyle.yahoo.com/new-idea/real-life/article/-/24170396/my-fight-for-life/

Mrs Lenik requires ERT (Enzyme Replacement Therapy ) to provide the enzyme which will act on the glycogen and allow it to enter the normal metabolic pathway that your cells use glycogen for.

Just one enzyme missing from the metabolic pathway can be fatal. It can be a problem in two ways : by causing a build up of the product at the step where the enzyme is missing, or by a lack of the product for the pathway, so the cell cannot carry on because this chemical is missing.

How do you get Two normal parents and a baby with a disorder OR two parents with disorder and a normal baby?

This can happen because the metabolic pathway that creates a phenotype has many steps on it, and a change to any one enzyme out of the chain can cause the disorder.

This question from the 2012 L2 exam is a great example.

What do you think is the best explanation?



[] This activity should reinforce your knowledge of functions of cell organelles.

[] After you have completed the Gene Interaction Punnett squares, this activity will help you memorise the ratio's.

[] Basic battleships to revise basic genetic language (yr 11 Science stuff).