CHAPTER 15:  GENE ACTIVITY

I. Phenotype = genotype + physical environment, through enzymes

            A. Sir Archibald Garrod introduced phrase inborn error of metabolism

 

                        1. Inherited defects could be caused by the lack of a particular enzyme

                        2. suggested link between genes and proteins

            B. 1940, Beadle and Tatum x-rayed spores of bread mold

                        1. mutated, some lacked an enzyme for growth on medium

                        2. one gene one enzyme hypothesis

                        C. Pauling and Itano compared hemoglobin in RBCs of sickle cell and

                             normal individuals

                        1. electrophoresis showed a difference in molecular size and charge

                        2. one gene - one polypeptide hypothesis

D. Ingram: change due to substitution of one amino acid

II. gene: a sequence of DNA bases that codes for a product

            A. nucleotide sequence of DNA determines amino acid sequence in proteins

            B. RNA: single-stranded, sugar ribose, base uracil instead of thymine

                        1. messenger RNA (mRNA) takes a message from DNA in nucleus to ribosomes in cytoplasm

                        2. Ribosomal RNA (rRNA) and proteins make up ribosomes where polypeptides are synthesized

                        3. Transfer RNA (tRNA) transfers a particular amino acid to a ribosome

III. how genes code for amino acids

            A. triplet code: made of 64 three-base code words (codons)

                        1. codon: 3 nucleotide bases of DNA or mRNA, codes for an amino acid

            B. Nirenberg and Matthei found an enzyme that made synthetic RNA, found first code

                        1. Degenerate code: 64 codons for 20 amino acids

                        2. unambiguous code: each triplet codon has only one meaning

                        3. there is one start codon and three stop codons

            C. universal code dates to first living organisms

IV. Transcription: mRNA, tRNA, and rRNA are transcribed from DNA templates

            A. promoter: on DNA, start of gene, direction of transcription, and strand copied

            B. a segment of DNA helix unwinds and unzips

            C. RNA polymerase forms complementary RNA nucleotides

                        1. nucleotides join together, mRNA elongates

                        2. terminator: stops transcribing DNA, releases mRNA transcript

            D. primary mRNA transcript is processed before leaving the nucleus

                        1. cap is put on 5' end telling a ribosome where to attach to begin translation

                        2. a poly-A tail is put on 3' end

                        3. introns are removed from mRNA before it leaves the nucleus

                                    a. intron: noncoding segment of DNA removed by spliceosomes

                                    b. exon: DNA code in mRNA that directs protein synthesis

                                    c. splicecomes: cut primary mRNA transcript, joins adjacent exons

                        4. the simpler the eukaryote, the less likely that introns will be present

                        5. ribozymes enzymatic RNAs that cut RNA at specific locations

                                    a. RNA could have served as both genetic material and as first enzymes in early life forms

                                    b. proof that RNA came before DNA

V. Translation: nucleic acid sequence is translated into protein in the cytoplasm

            A. tRNA transfers amino acids to the ribosomes

                        1. anticodon nucleotides on tRNA are complementary to codon on mRNA

                        2. at least one tRNA molecule for each amino acid, some pari with more than one codon

                        3. tRNA synthetases recognize which amino acid should join which tRNA

            B. rRNA is produced off a DNA template in the nucleolus

                        1. rRNA subunits move separately through nuclear pores to form ribosomes

                        2. ribosomes can float free in cytosol or attach to endoplasmic reticulum

                        3. ribosomes have binding sites for mRNA and tRNA

                        4. translation terminates once polypeptide is formed

                        5. polyribosomes: clusters of several ribosomes synthesizing the same protein

            C. mRNA codons base pari with tRNA anticodons carrying specific amino acids

                        1. codon order determines order of tRNA and sequence of amino acids

                        2. enzymes are required for all three steps

                        3. chain initiation: small ribosomal subunit attaches to mRNA near start codon

                        4. chain elongation: adds new amino acids and links them to previous ones

                        5. chain termination: occurs at stop codon

VI. gene mutations: alterations in nucelotide sequence of DNA

            A. frameshift mutations: when one or more nucleotides are inserted or deleted from DNA, ex) THE CAT ATE THE

                RAT  -> THE ATA TET HER AT

            B. point mutations: changes a single nucleotide, or a single codon

                        1. silent mutations: show no effect, UAU to UAC, both code for tyrosine

                        2. nonsense mutation: change UAC to UAG (stop), makes a shorter protein

                        3. missense mutation: change UAC to CAC, histidine instead of tyrosine

            C. mutations due to DNA replication errors are rare

                        1. common mutagens: radiation, organic chemicals, pesticides, smoke

                        2. if mutation is in gametes, then offspring may be affected

                        3. if the mutation is in the body cells, then cancer may result

                        4. everyone is exposed to UV radiation, it penetrates skin and breaks DNA

                            of underlying tissues

                                    a. when 2 thymine molecules are near each other, join as dimers

                                    b. usually dimers are removed by repair enzymes

                                    c. lack of repair enzymes produces xeroderma pigmentosum, giving a higher incidence of

                                        skin cancer