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DNA is universal The DNA in all organisms has the same basic structure. The nucleotides with their 4 bases Adenine Thymine, Cytosine and Guanine are all the same. The only difference is the order in which they are put together in different organisms. 12 BIOLOGY, CH 8 2 Watson and Crick model of DNA 12 BIOLOGY, CH 8 3 12 BIOLOGY, CH 8 4 Watson and Crick model of DNA Using these results and other accumulated evidence, Watson and Crick suggested that DNA consisted of the now familiar two chains twisted around each other to form a double helix ladder, crosslinked by nitrogenous bases. 12 BIOLOGY, CH 8 5 From DNA to Proteins DNA codes for the production of proteins. Proteins (enzymes) determine the reactions that occur in a cell and other proteins determine some of its structural characteristics. Proteins differ from each other in the sequence of the 20 amino acids and the length of the polypeptide chain. 12 BIOLOGY, CH 8 6 From DNA to Proteins Since there are only 4 different nucleotides in DNA and they need to code for 20 amino acids, the code must be in triplets (AGC, TGA, etc.) called codons. 12 BIOLOGY, CH 8 7 Transcription – formation of mRNA The code on the DNA has to get from the nucleus to the ribosomes in the cytoplasm. The DNA itself does not leave the nucleus. The DNA is transcribed into mRNA which then leaves the nucleus and attaches to the ribosomes. 12 BIOLOGY, CH 8 8 Comparison of DNA and RNA 12 BIOLOGY, CH 8 9 Comparison of DNA and RNA 12 BIOLOGY, CH 8 10 Transcription – formation of mRNA The DNA in the relevant region first unwinds, and then unzips. Only one of these strands is used to direct the synthesis of mRNA; this is called the template strand. The other strand of DNA is called the non-template strand. A particular nucleotide sequence at the beginning of the gene, called a promoter, signals the start of a gene. Proteins position RNA polymerase on to the DNA to bind with the promoter. 12 BIOLOGY, CH 8 11 Transcription – formation of mRNA Complementary RNA nucleotides are progressively joined together by RNA polymerase moving along the length of DNA. A base sequence at the end of the gene serves as a stop signal. The mRNA is released as a single strand. The DNA zips up and twists itself back into a double helix again once the mRNA has peeled off. 12 BIOLOGY, CH 8 12 Pre-mRNA to mRNA The mRNA strand at this stage is called pre-mRNA. Before it leaves the nucleus it is modified by the addition of: a methylated cap at the 5’ end and about 100–200 adenine nucleotides at the 3’ end. Most eukaryotic genes have regions of base sequences (introns) that are not translated into proteins. Exons contain the actual information for protein formation. The introns are removed, and the mRNA leaves the nucleus. 12 BIOLOGY, CH 8 13 SRAM 208: “Transcription” 12 BIOLOGY, CH 8 14 Translation – mRNA into Proteins When mRNA moves into the cytoplasm, it attaches itself to a ribosome, where it causes amino acids to assemble in a particular order. 12 BIOLOGY, CH 8 15 Translation – mRNA into Proteins Ribosomes are made up of two subunits, one small and one large. The nucleus assembles them both from ribosomal RNA (rRNA) and proteins. The subunits move from the nucleus into the cytoplasm, where they combine to form the functional units of translation. 12 BIOLOGY, CH 8 16 Translation – mRNA into Proteins Another type of RNA, called transfer RNA (tRNA), is also needed for protein synthesis. tRNAs carry amino acids to ribosomes. They do not have a linear arrangement of nucleotide bases but are folded back on themselves to form a compact three-dimensional structure rather like a clover leaf. 12 BIOLOGY, CH 8 17 Translation – mRNA into Proteins The three nucleotide bases at the bottom of the molecule make up the anticodon. There is an amino acid binding site at the top of the molecule. The symbols D, Ψ and T represent unusual nucleotides that are characteristic of tRNAs. Base pairing only occurs in certain regions. 12 BIOLOGY, CH 8 18 Translation – mRNA into Proteins The anticodon of the t RNA is complementary to the codon of the mRNA. The type of amino acid picked up by tRNA is related to the sequence of the anticodon. For example, a tRNA molecule with the anticodon ACG will pick up a cysteine amino acid on its binding site by means of an enzyme. 12 BIOLOGY, CH 8 19 Translation – mRNA into Proteins The ribosome bonds to the methylated cap on the mRNA and moves along it ‘scanning’ for an AUG start. The ribosome passes along the mRNA strand and, as it passes each codon in the mRNA, a tRNA, carrying the appropriate amino acid, moves to the ribosome. The codon in the mRNA bonds to the complementary anticodon in the tRNA molecule. The ribosome moves to the next codon of the mRNA strand, another tRNA molecule with a corresponding anticodon brings another amino acid into position, and so on. Once the job of the tRNAs is complete, they detach themselves from the mRNA and return to the pool of tRNAs in the cytoplasm, from where they can be drawn upon again when required. The amino acids are linked to form a polypeptide chain in an order corresponding to the sequence of base triplets in the mRNA, and therefore the DNA. 12 BIOLOGY, CH 8 20 Translation – mRNA into Proteins Meanwhile other ribosomes are carrying on the same process, moving along the mRNA strand simultaneously, each synthesising a polypeptide chain as it goes. (see Animation “Polyribosome”) 12 BIOLOGY, CH 8 21 Translation – mRNA into Proteins 12 BIOLOGY, CH 8 22 Summary 12 BIOLOGY, CH 8 23 The Genetic Code The genetic code shows the relationship between the triplets of bases in mRNA (i.e. the codons) and the amino acids that are translated from the mRNA code. From this, it is possible to work out the relationship between the bases in the original DNA and the amino acids that result. Most of the amino acids are coded for by more than one codon. Thus, the code contains more information than is actually acted on in the cell (the code is redundant). Three of the codons do not actually code for an amino acid, but they stop the polypeptide chain at that point, acting as termination signals. These stop codons play an essential role in the cell, allowing polypeptides of precisely the right length to be produced. 12 BIOLOGY, CH 8 24 The Genetic Code 12 BIOLOGY, CH 8 Also see SRAM 193 25 Interactive site: http://learn.genetics.utah.edu/units/basics/transcribe/ Dustbin game: http://www.classtools.net/my/dustbin89919TESTER.htm Whole Process: http://www.uic.edu/classes/bios/bios100/lecturesf04am/lect14.htm SRAMs: “Translation” “Review of Protein Synthesis” “Genes to Proteins” “Analysing a DNA Sample” 12 BIOLOGY, CH 8 26 X 12 BIOLOGY, CH 8 27 Gene Regulation in E.coli E.coli can break down glucose or lactose to obtain energy. E.coli can turn lactose metabolism on or off by turning the genes that code for the enzymes on or off. 12 BIOLOGY, CH 8 28 The lac operon consists of an operator (the binding site for the repressor protein), a promoter (binding site for RNA polymerase) and three genes that code for enzymes involved in lactose breakdown. A repressor protein regulates the three genes by binding to the operator and inhibiting transcription. 12 BIOLOGY, CH 8 29 Lactose is a signal molecule or inducer. If lactose is present, it binds to the repressor, altering its shape so that it cannot bind to the operator. The RNA polymerase is able to transcribe the three genes which are then translated into the three enzymes. 12 BIOLOGY, CH 8 30 If lactose is absent, or low, the repressor protein is able to bind to the operator, covering part of the promoter. This means that RNA polymerase cannot bind to the promoter and transcription of the genes is blocked.. 12 BIOLOGY, CH 8 31 Gene Regulation in Eukaryotes Gene regulation is far more complicated in eukaryotes than in prokaryotes, particularly when multicellular eukaryotes are considered. For instance, enhancers are regions found in eukaryotic DNA that act as binding sites for some activator proteins. They seem to act by increasing the number of RNA polymerase molecules transcribing the associated gene. Chemical modification also seems to exert control over gene expression. 12 BIOLOGY, CH 8 32 Watch video clip “Genetic switch” >> 12 BIOLOGY, CH 8 33 VARIATION Variation in genetic material can result from: Independent Assortment of chromosomes during meiosis (metaphase 1) Crossing over during meiosis (metaphase 1) Random fertilisation of ova by sperm Mutations 12 BIOLOGY, CH 8 34 MUTATIONS Mutations are changes to the DNA by: Addition Deletion Rearrangement Mutations can occur on individual genes or on chromosomes Mutations can occur in somatic cells or in germ-line (sex) cells SRAM 259, 2012: “The Effect of Mutations” 12 BIOLOGY, CH 8 35 Gene Mutations Most gene mutations occur during DNA replication and are usually repaired by enzymes, but sometimes they are not. When a single DNA nucleotide base changes, it is referred to as a point mutation. Some changes can involve more than one nucleotide. The changes usually have an effect on protein synthesis. 12 BIOLOGY, CH 8 36 Gene Mutations Substitution a nucleotide is replaced by another type (e.g. adenine substituting for guanine) This has a number of possible effects: • The new codon still codes for the same amino acid as the original codon (e.g. GAG and GAT both specify for the addition of a leucine amino acid in a polypeptide chain). This is an example of a neutral (or silent) point mutation. • The new codon codes for a different amino acid, but a functional protein is still produced, although it is slightly different. The new codon codes for a different amino acid but the resulting polypeptide is non-functional. The new codon may even specify a codon for ‘stop’, which would shorten the length of the whole protein, making it non-functional. 12 BIOLOGY, CH 8 37 Gene Mutations INSERTION and DELETION The addition or deletion of one or two nucleotides in a gene sequence normally has a major effect on the polypeptide produced because it is a frameshift mutation. Every codon after the insertion or deletion changes because nucleotides are read in groups of three. This is illustrated by the addition of the letter S before the word ‘PIE’ in the sentence: KIM ATE THE SPI EFO RTE A or the deletion of P from PIE: KIM ATE THE IEF ORT EA. 12 BIOLOGY, CH 8 38 12 BIOLOGY, CH 8 39 Gene Mutations SRAMs: 243, 2013 “Gene Mutations” 244, 2013 “Sickle Cell Mutations” 12 BIOLOGY, CH 8 40 Chromosome Mutations Chromosome mutation may result from: Deletion (sections of a chromosome are missing and therefore some genes are missing) 12 BIOLOGY, CH 8 41 Chromosome Mutations Inversion (part of the chromosome breaks off, rotates 180˚ and rejoins). 12 BIOLOGY, CH 8 42 Chromosome Mutations Translocation (part of one chromosome breaks off and joins onto another non-homologous chromosome) 12 BIOLOGY, CH 8 43 Chromosome Mutations Duplication (part of a chromosome is duplicated and added onto the same chromosome) 12 BIOLOGY, CH 8 44 Chromosome Mutations Aneuploidy The chromosome number is more or less than that in the normal diploid or haploid cell. Results in the addition or loss of whole chromosomes from a cell. Normally in meiosis, homologous chromosomes come together and then segregate into separate cells, so that the gametes finish up with only one of each pair of chromosomes. However, on some occasions the two homologous chromosomes, instead of separating, go into the same cell. This phenomenon is known as non-disjunction. 12 BIOLOGY, CH 8 45 If the gametes with both copies fertilise a normal cell, the zygote will have three copies of the chromosome. This is called Trisomy. Trisomy 21 results in Down Syndrome. 12 BIOLOGY, CH 8 46 12 BIOLOGY, CH 8 47 Chromosome Mutations Abnormalities in sex chromosomes Non-disjunction also causes various sex chromosome abnormalities in humans. XXY – Klinefelter syndrome. This may result either from the fusion of a Y sperm with an XX egg or from the fusion of an XY sperm with an X egg. Although XXY individuals are phenotypically men, they have very small genitals and are infertile; in addition, they may develop breasts, but testosterone therapy at puberty can often help alleviate the symptoms. Turner syndrome is due to the absence of one of the sex chromosomes. OY individuals never survive to birth. XO individuals are infertile females. XYY - Jacob syndrome males tend to be taller than average and may be mildly mentally retarded. 12 BIOLOGY, CH 8 48 Chromosome Mutations Polyploidy: When cell division fails altogether, half the gametes have two of each type of chromosome (i.e. being diploid) and the rest having none. If a diploid gamete fuses with a normal haploid gamete, the resulting individual is triploid – (it has three of each type of chromosome). If two diploid gametes fuse, a tetraploid individual results. Polyploidy occurs when an organism has one or more complete extra sets of chromosomes. Polyploidy is rare in animals but common in plants. Polyploidy is lethal in humans. 12 BIOLOGY, CH 8 49 Chromosome Mutations Seedless grapes (and other fruit) are the result of polyploidy and are infertile. 12 BIOLOGY, CH 8 50 Chromosome Mutations SRAMs: 246, 2013 “Chromosome Mutations” 248, 2013 “Non-disjunction in Meiosis” 249, 2013 “Aneuploidy in Humans” 12 BIOLOGY, CH 8 51 Chromosome Mutations Sites on Mutations: http://www.biozone.com.au/biolinks/GENETICS.html#D4 12 BIOLOGY, CH 8 52 The Selfish Gene “We are survival machines - robot vehicles blindly programmed to preserve the selfish molecules known as genes. This is a truth that still fills me with astonishment.” The Selfish Gene Richard Dawkins 1941- English biologist 12 BIOLOGY, CH 8 53 Heredity “Heredity provides for the modification of its own machinery.” James Mark Baldwin, 1896 GEENOR's comment: now we have genetic engineering, which can do the same. 12 BIOLOGY, CH 8 54