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Chapter 8 DNA: the universal molecule of life All living things share the same genetic code – DNA. Three consecutive bases (or nucleotides) called triplets in the DNA molecule carry the code for 1 amino acid in a polypeptide chain. Arrangement of the nucleotides determines the proteins produced. Discovery Many scientists experimented & tried to work out the composition & structure of the ‘heredity’ molecule. Watson & Crick used their information to describe the current model of 2 twisted chains producing the double helix, cross linked with nitrogen bases adenine (A), cytosine (C), guanine (G) and Thymine (T). From DNA to Proteins • DNA contains the code to make all the bodies proteins - polypeptides made of linked amino acids. • The order in which amino acids (20 different kinds) are linked, and relative abundance of each determines the functionality of the protein. • 3 bases codes for 1 amino acid. This triplet of bases is called a codon. • The code has to get from the chromosome to the ribosomes that produce the protein. Messenger RNA (mRNA) carries a copy of the code from the chromosome, through the cytoplasm to the ribosomes in a process called transcription. • Ribosomes consist of 2 sub-units (1 small, 1 large) of ribosomal RNA, (rRNA) and proteins assembled in the nucleus, they move into cytoplasm and combine to form ribosomes. Transcription • A section of DNA with the required gene unwinds and unzips (with help of RNA polymerase) • Enzyme RNA polymerase binds to promotor region on the gene - joins complementary nucleotides that attach to exposed bases on the template DNA strand – (C to G, A to T, U to A (U not T is in RNA) to make a complimentary strand of pre-mRNA. • Not all the DNA segments in a gene translate to protein –introns are cut from the mRNA before it leaves the nucleus. Exons - sections of gene that do code for proteins are spliced back together. • This post translation modification includes the intron cutting, addition of a methylated cap and a poly-A tail to allow movement out of the nuclear membrane and results in mRNA Translation • mRNA moves from nucleus to ribosomes where the code is translated into a protein. • Each codon (sequence of 3 bases) in the mRNA codes for a particular amino acid, or is a start (AUG-methionine, met) or stop codon (UAA, UAG, UGA). • Transfer RNA (tRNA) molecules carry a different amino acid at one end, and a 3 base sequence (anticodon) at the other end. • Anticodons bond with complimentary codons in the mRNA. 1. A small ribosome sub-unit moves along a section of mRNA looking for a start codon (promoter), it’s then joined by a large ribosome subunit. 2. Start codon initiates protein building by putting met in the1st amino acid position. 3. Ribosome moves along mRNA coordinating the bonding of tRNA anticodons to mRNA codons. 4. Amino acids carried by the tRNA are linked by peptide bonds to produce a chain, tRNA released. 5. Stop codon ends the process and the polypeptide chain is released. The Genetic Code • Complete genetic code was determined 1966 –codon / AA relationship, 3 stop codons • Universal genetic code to all living things same process DNA, mRNA, tRNA etc. • DNA – universal indicator of life. Text Questions – 1, 2, 4, 7, 8, 9, 11, 12 Biozone – 206 – simplest case genes -> proteins, 209 Transcription, 210 translation, 202 replication review or do it if you didn’t do it for chapter 7 Gene regulation - ‘switching on and off’. All cells contain the full genome -all genes are not expressed in cells at all times. Genes are expressed in different cell types, at different times & rates, in different conditions & life stages. • Structural genes produce proteins for structure and function in an organism. • Regulator genes produce proteins to control the action of other genes – turn them ‘on’ or ‘off’. o DNA binding proteins bind to regions of DNA near the gene and switch them on or off. o Signalling proteins bind to cell membrane receptors in target cells & trigger reactions that switch genes on or off. o Homeotic genes control the orderly events occurring in embryonic development. Post translation modification of mRNA can result in alternative splicing where different sections of the gene are cut out, some introns may be retained, some exons removed. This could result in different proteins being produced from the same gene in different conditions. Text questions – 13, 14, Variation – new combinations of alleles, DNA mutations, multiple alleles, polygenes, environment Chromosomal -Crossing over and fertilisation increase variation by changing allele combinations Mutations – changes to base sequences in DNA. Can be neutral, beneficial or harmful. Somatic mutations are not inherited. Germ line mutations occur in gamete DNA and can be inherited. Point mutations involve 1 base in a gene Frame shift mutations change every codon after the mutation - major effect on polypeptide produced. • Deletion of a base changes the amino acid sequence from that point on –major change to protein • Addition/ insertion of a base changes the amino acid sequence from that point on – major change to protein • Substitution of a base changes the amino acid coded for at that point, some may have little effect, as the new codon may still code for the same AA, some may have a major effect. • Inversion where 2 nucleotides reverse. No difference if it’s the same nucleotide, similar to substitution if different nucleotides. Chromosome mutations or block mutations involve changes to whole segments of a chromosome • Deletion- a piece of chromosome drops out and the chromosome rejoins producing a shorter chromosome. Major affect as genes have been lost, most deletions are fatal unless very short. • Inversion – section breaks out and reverses, normal gene sequence reverses • Translocation – section breaks out and attaches to another chromosome • Duplication-section of chromosome replicates, often many times, often harmful • Aneuploidy – chromosomes missing or extras present. -non disjunction - homologous chromosomes fail to segregate and stay together - move into the same gamete resulting in 1 with an extra chromosome, 1 missing a chromosome. Down’s Syndrome - trisomy 21 (3 chromosome 21). Klinefelter syndrome – XXY, (XX and Y or XY and X gametes), Turner syndrome -XO • Polyploidy –extra whole sets of chromosomes. Triploid 3sets, tetraploid 4 sets. Lethal in humans but common in plants Causes of mutations • Occur naturally but increased by mutagens - high temperatures, chemicals, radiation Main ideas about mutations 1. Mutations arise spontaneously, environment can influence rate of mutation but not cause them 2. Mutations are persistent, transmitted through many generations 3. Many mutations are disadvantageous but sometimes they are advantageous. Text Questions 15, 19, 20 Biozone – 256 mutations, 257 effect of mutations, 258 harm or benefit, 260 (read) cancer, 261 gene mutation, 262 point mutation 265, chromosome mutations, 263/4 read cases -sickle cell, CF