* Hereditary: these molecules are passed from generation to generation.

Transcription

1 D) Nucleic Acids - Genetic Material: Carry the info to make proteins act as a blueprint. * Hereditary: these molecules are passed from generation to generation. - Largest molecules in body. - All have a C, H, O, N and a P (phosphate).

2 A. Building Blocks = NUCLEOTIDES - A central pentose sugar with a phosphate and a nucleobase attached. * They can have a ribose or a deoxyribose sugar. * There are 5 different bases, so there are 5 different nucleotides ADENINE (A) GUANINE (G) CYTOSINE (C) THYMINE (T) URACIL (U) * Chemically, A & G are called PURINES, while T, C and U are PYRIMIDINES Nucleotide: Nucleic Acid: B. The Macromolecule: Nucleic Acids - Polymers of Nucleotides Sugar-Phosphate backbone with nucleotide bases sticking out (free to form bonds). Keeps going:

3 They are very long. The sequence of the nucleotides can be in any order. It is the bases that make up the genetic code instructions for making the polypeptides.

4 C. Base pairings between the nucleotide bases. - The bases can begin to form bonds. These bonds can become crossbridges between chains. * They are hydrogen bonds. * Sometimes these cross bridges are long-term connections, sometimes they are short-term. * So even though the simple alpha helix chain is a basic nucleic acid, we can start to get more complex structures. - These cross bridges between bases are very specific. Base Pairings: A and T bind to each other, C and G bind to each other. A never binds to C or G. T never binds to C or G. Etc.. A can also bind to U. That will become important when we talk about RNA. Okay, the molecules form specific bonds. And these can become cross-bridges. So what? It is this specificity of the bonding, what we call BASE PAIRS (A to T, and C to G) that gives nucleic acids all the special characteristics they need to act as the genetic material, and the hereditary material.

5 Because of these specific base pairings, the nucleic acids can: 1. Act as a template to make other molecules. Sequence of second strand is pre-determined! Take the top strand 2. Replicate themselves. Through the same process we saw in Step 1 above! Take the top strand 3. Code for proteins. Overly simplistic examples here. More detail later where needed. Special cellular machinery uses basically same method (attaching to specific bases) to form a polypeptide!

6 - 2 major classes of nucleic acids: 1. DNA - deoxyribonucleic acid (Let s break that down): de oxy ribo nucleic acid Without has a ribose and a nitrogen-base oxygen sugar acid * Polymer of nucleic bases "A" "G" "C" and "T" ** Forms a double-stranded, alpha helix molecule. If unwound, you see how the sequence of bases could be used as "letters", which can form "words". The ribosome can follow these instructions, laying down amino acids in the correct sequence! The Genetic Code: THE SEQUENCE OF BASES IN DNA CODES FOR THE SEQUENCE OF AAs IN PROTEINS!!

7 - In our cells, this is the primary genetic information (the Genetic Material). It is protected within the nucleus. * Notice what a stable structure we have made. Sugar-phosphate backbone, coiled into an alpha-helix, and double-bound strands. It must be un-wound to be used. *To make it even more secure while it is in the nucleus, we wrap it around histones to form Chromatin (DNA + proteins). It is also our hereditary material. * Remember: It can be duplicated. So future generations of cells can get copies of the instructions when cells replicate & divide (process of mitosis see later in cell chapter)! *To make it even more stable & secure as we move it between generations, we super-coil it into a Chromosome.

8 - Some terms that can be confusing: DNA = the macromolecule double-stranded helix Genes are found along the DNA molecule. Genes are not a molecule! Chromatin: the DNA molecule wrapped around Histone proteins. The genetic info cannot be used while in this state. The chromatin must be unwound to use it! See later! Chromosome: a highly condensed version we only see during mitosis (which occurs during cellular division). The material has been replicated, and we super coil it to make it easier to handle! Chromosomes have 2 sister chromatids ( replicants ) held together in a centromere.

9 2. RNA - ribonucleic acid (has an oxygen on the ribose sugar). - Uses "U" instead of "T" * Forms a single-stranded alpha helix. This is the molecule actually used by the cellular machinery for protein synthesis, thereby protecting the DNA. Codon: sequence of 3 nucleotide bases ( Triplet ) contains information for 1 AA in primary sequence of protein (see later). Gene: (alternate way of looking at a gene): sequence of codons that code for 1 polypeptide (start to finish). - Four big differences between DNA and RNA: 1. The sugar in DNA is deoxyribose; in RNA it is ribose 2. The nitrogenous base uracil (U) is used in RNA in place of T (they are very similar bases; in RNA U= A just like T = A.) 3. DNA is a double helix, found in the nucleus. RNA is single stranded AND # 4: In our cells - DNA is the HEREDITARY INFO (passed through generations). RNA will be used by the cellular machinery to actually make the polypeptides, thereby protecting the DNA.

10 PLEASE NOTE: C. Function of the Nucleic Acids At the end of this section we will have a summary of these processes (characterized by yellow boxes), which will help you get ready for the exam! You should concentrate on knowing the summary, and the definitions of any boldfaced terms in this section. - Both = involved in PROTEIN SYNTHESIS (synthesis = production or making. NOTE: Part of this info might be in the "Cell Chapter", while other pieces of info might be in a separate "Genetics" chapter. I combine them here; you are only responsible for the material as presented here. Also note: We are going to cover how these molecules work in mammals. This is not universal! Last Note: I am not going to talk about all the different kinds of RNA (there are several). I am going to give you a simple model to start from. Depending on your instructor, there may be more detail you are responsible for on an exam. This is a quick review and outline: 1. The Gene & The Central Dogma: How is the information in DNA turned into Protein? - DNA is a huge molecule that carries the complete set of instructions for making all the proteins a cell will ever need! * Each cell has the entire set of info, but only uses a small sub-set. Beta cells of pancreas make insulin using that part of the code, while the acini cells of the pancreas make digestive enzymes using another part of the code. - Gene: The DNA in each piece of chromatin that provides the instructions for a protein is called a gene. * Although there are only four different bases in DNA (A, C, G and T), the order in which the bases occur determines the information to make a protein, just like the 26 letters of the alphabet combine to form words and sentences in English: Compare English: RAT - TAR ART Same 3 letters; completely different meanings. To DNA: GAC - AGC - CGA Same 3 'letters'; completely different meanings to the cell (specifies the amino acids Aspartic Acid, Threonine, and Arginine) KEY WORD: SEQUENCE is very important to meaning!

11 - Do not directly use the genetic material (genes) in the DNA; too valuable. * Instead, use a "messenger" to carry the instructions from DNA out into the cytoplasm. A nucleic acid very similar to DNA, called mrna or messenger RNA, is a copy of a gene, and serves this function the "bridge" between DNA and protein: The Central Dogma: Genetic information always goes form DNA to RNA to protein.

12 2. Transcription = Re-writing DNA into RNA - Transcription: The order of the bases in the DNA specifies the order of bases in the mrna. Occurs in the nucleus. - DNA is "transcribed" or re-written into RNA in a very complicated process called transcription. * to "transcribe" means to write something down, or make a copy. - Simply stated, during transcription, one gene (DNA) is 're-written' into an RNA in the nucleus: A team of enzymes and proteins binds to the promoter, or starting region, of a gene. The enzymes use one of the DNA strands to make an RNA copy of that one gene. This copy, which contains the instructions to make 1 protein, is called an mrna or messenger RNA. After the mrna is made, it is shipped out of the nucleus through a pore. 3. Translation: De-coding RNA into protein ("different language") Translation: The order of bases in the mrna specifies the order of amino acids in a protein. Occurs in the cytoplasm During translation, the mrna transported to the cytoplasm is "de-coded" or "translated" to produce the correct order of amino acids in a protein: The Primary Sequence of the Protein (see earlier). * Translation requires numerous enzymes, but we will just talk about the ribosome. - The genetic code is a triplet code: (1) Nucleotides on mrna are read "three at a time" by the ribosome. Every three nucleotides in an mrna (a 'codon') specify the addition of one amino acid in a protein. All proteins start with the initiation (start) codon AUG STARTS HERE! (There are other start codons, but this one is universal among all life! See below discussion on Unity of Life ).

13 There are stop codons : RIBOSOME STOPS PRODUCING PROTEIN The codons between "start" and "stop" tell the ribosome which is the next Amino Acid in the polypeptide chain. (2) The amino acids corresponding to all 64 codons have been determined = we cracked the genetic code! The genetic code chart represents the sequence on the mrna codon. All living organisms and viruses use this triplet genetic code - "biological unity"!!! The code is nearly identical for all known life forms, from bacteria to animals and plants. Exception: Mitochondria (the organelle - see Cell Chapter) makes its own protein, following a different genetic code. Notice The Redundancy! - The same mrna may be used hundreds of times during translation by many ribosomes before it is degraded (broken down) by the cell. Now you see why we don't use the original DNA! INTERESTING NOTE: after the AAs are laid down, the folding of the protein into its secondary and tertiary structure are NOT left to chance. Special proteins called "Chaperone proteins" help them fold correctly. Scanning electron micrograph of ribosomes performing translation on an mrna molecule.

14 IV. Mutations & an Intro to Heredity - We have seen that nucleic acids can duplicate itself & act as a template due to the specific base pairings. Our cells are constantly duplicating it (before cellular division) and using it for translation. Note to student: there is a review here. No notes are needed for the review. * But, mistakes happen in both these processes. - MUTATION: Random change in the sequence of the DNA might lead to a change in the codon on the mrna, and therefore a change in the sequence of the AAs in the protein. Recall: * Why? Accidental chemical changes, radiation causes, chemical change, or other reasons. Most are simple mistakes in genetic replication before cellular division. - Small change in AA sequence can have one of 3 consequences: 1. No effect. New AA doesn't change overall shape of the polypeptide very much. MOST COMMON. We all have small genetic differences between us that do not matter. Alleles: different versions of the same gene (or product of that gene the protein) e.g.: there are 3 functioning alleles of Hemoglobin: HbA, HbA2, & HbF

15 2. Bad effect: Mutation in code leads to AA sequence change, which changes the shape of the protein in such a way that the resulting protein loses its function. Might lead to a PATHOLOGY. The mutation is "deleterious". * About 20% of all mutations are deleterious. Average human has an estimated 2000 mutations that would lead to a pathology. Why don t we die from this? Because most mutations do not matter. Redundancy in genetic code (no change in AA sequence), or they do not significantly change resulting polypeptide, maybe do not affect active site, etc. 3. Mutation leads to an imporvement: so incredibly rare, that this never happens. - Somatic Mutations: Changes in the genetic code of existing cells. Estimated that we have trillions of these mutations daily. Most do not matter, as we have trillions of cells. Exceptions: Some cancers (minority), some other diseases BUT RARE. - Inherited mutations: those that occur in gamettes have more potential for pathology. Genetic Disease. Still rare, however, as we are protected. Because we have 2 sets of all our genes. Only if the mutation is deleterious

16 - We have 2 sets of chromosomes (HOMOLOGOUS chromosomes - they carry the same genes): one from mom (maternal chromosome), one from dad (paternal chromosome) - we have an EXTRA COPY of each gene! We have 46 chromosomes, but it is better to think of them as 23 homologous pairs, as they duplicate each others genes. HOMOZYGOUS: you have the same copy from each parent HETEROZYGOUS: you have a different copy from each parent There are 2 types of heterozygotes: Scenario #1: Different but still functional Scenario #2: Different and one doesn t function! Sexual reproduction helps protect us against genetic mutations.

17 - A bad mutation gotten from 1 parent can be made up by the copy gotten from the other parent. * CARRIER a heterozygote where one of the variants is deleterious Heterozygotes for deleterious traits are "carriers", because they don t have the disease, but the can pass the trait to the next generation. carrier For most genetic disease, the offspring must me HOMOZYGOUS for the deleterious mutation. In other words, got a copy from both parents. Not always true: dominant genes superceed recessive genes. Dominant genes person has the trait with only 1 copy. True of both deleterious and nondeleterious traits, like hair color. Recessive genes: More common condition. You need 2 copies to show the trait. If the deleterious mutation is dominant, only need one to hae the genetic disease. Super rare because they are so deadly. Know these terms for the exam: Mutation Deleterious mutation Somatic mutation Allele most are not deleterious Inherited mutation - gamette Homologous chromosomes 23 pairs Homozygote Heterozygote - different versions of the gene Carrier - one of them is deleterious Dominant trait Reccesive trait Codominance

18 V. Important terms and concepts for the exam - Your genetic material codes for proteins. It is the hereditary material (passed to you directly from your parents). So, the ability to make the correct proteins is passed from one generation to the next generation. 1. Gene (genetic info to make one polypeptide). 2. Chromosome and Chromatin - molecule carrying the Genetic info. 3. Nucleotide bases: ATCG and U - purines & pyrimidines. * Genetic code is the sequence of bases on DNA 4. Nucleic Acids: DNA & RNA. * Know the differences between these 2 molecules. 5. Transcription: sequence of bases on DNA dictates sequence of mrna in nucleus. Done by various enzymes in nucleus. * mrna has "start sequence", then "codons (triplets), then a "stop sequence". 6. Translation: Sequence of bases on mrna dictates primary sequence of Amino Acids, which thereby determines the proteins tertiary shape and therefore overall function (see protein section). * Done by various enzymes and ribosome in cytoplasm. Ribosome strings along the AAs, using dehydration synthesis, following the codons in the mrna. 7. Genetic code - a listing of all the 3-nucleotide sequences on the mrna (Codons) and their corresponding AAs on the polypeptide chain. 8. Mutation - change in nucleotide sequence. 9. Heterozygous = different on the 2 homologous chromosomes, homozygous = same on the 2 homologous chromosomes. 10. Carrier = a heterozygote that has a "bad copy" of a gene (="deleterious")