CHAPTER 18 GENE EXPRESSION AND PROTEIN SYNTHESIS
The Flow of Genetic Information • Genes are segments of DNA that contain information necessary for the synthesis of proteins.
Transcription • Transcription: the process by which information encoded in a DNA molecule is copied into an mRNA molecule. • Transcription starts when the DNA double helix begins to unwind near the gene to be transcribed. • Only one strand of the DNA is transcribed. • Ribonucleotides assemble along the unwound DNA strand in a complementary sequence. • Enzymes called RNA RNA polymerases catalyze transcription
RNA nucleotides RNA polymerase Newly made RNA Direction of transcription Template strand of DNA (a) A close-up view of transcription
Splicing • Introns are removed, exons are joined together producing mRNA which then exits the nucleus.
DNA Transcription-DNA to RNA RNA mRNA Translation- RNA to protein Protein
DNA molecule Codon-group of 3 nucleotides that codes for 1 amino acid Gene 1 Gene 2 Gene 3 DNA strand Transcription RNA Codon Translation Polypeptide Amino acid Figure 10.10
The Genetic Code • The genetic code is the set of rules relating nucleotide sequence to amino acid sequence Figure 10.11
Features of the Code • All 64 codons have been assigned. 61 code for amino acids. • 3 (UAA, UAG, and UGA) serve as termination signals. • More than one triplet can code for the same amino acid; Leu, Ser, and Arg, for example, are each coded for by six triplets. • The code is almost universal: it the same in viruses, prokaryotes, and eukaryotes.
Transfer RNA (tRNA) • tRNA Amino acid attachment site • Acts as a molecular interpreter • Carries amino acids • Matches amino acids with codons in mRNA using anticodons Hydrogen bond RNA polynucleotide chain Anticodon Anticodon Figure 10.15
Ribosomes • Are organelles that actually make polypeptides • Are made up of two protein subunits • Contain ribosomal RNA (rRNA) Figure 10.16a
Translation • Translation: the process whereby a base sequence of mRNA is used to create a protein. • There are four major stages in protein synthesis: • Activation • Initiation • Elongation • Termination
Amino Acid Activation • The activated amino acid is bound to its own particular tRNA by an ester bond between the carboxyl group of the amino acid and the 3’-OH of the tRNA.
Termination Fig. 26-9, p. 673
Mutations and Mutagens • Mutation: a heritable change in the base sequence of DNA. • Occur during DNA replication or be induced by environmental factors • Mutagen: a chemical that causes a base change in DNA. • Not all mutations are harmful. • Certain ones may be beneficial because they enhance the survival rate of the species.
Mutations • point mutation Normal hemoglobin DNA Mutant hemoglobin DNA mRNA mRNA Sickle-cell hemoglobin Normal hemoglobin Glu Val Figure 10.21
FRAMESHIFT MUTATIONS • Insertions and deletions • Usually have disastrous effects • Change the reading frame of the genetic message mRNA Protein Met Lys Phe Gly Ala (b) Nucleotide deletion Met Lys Leu Ala His Figure 10.22b THE FAT CAT ATE THE RAT -->delete first "E"--> THF ATC ATA TET HER AT...
Huntington disease (HD) • Inherited neurological disease that leads to dementia • About 30,000 Americans have HD • The gene, whose mutation results in Huntington disease, codes for the protein huntingtin. • In this disorder, the trinucleotideCAG is repeated, which adds a string of glutamines (Gln) to the encoded protein.
Because glutamine is a polar amino acid, the overabundance of glutamine causes links to form within and between proteins. • Altered huntingtin proteins “stick” to one another, forming strands that are held together by hydrogen bonds. • Rather than folding into functional proteins, they develop into tangled, rigid groupings known as protein aggregates. • These fibrous protein aggregates accumulate and interfere with nerve cell function. -CH2-CH2-C-NH2 ║ O
Cystic Fibrosis (CF) • CF is caused by a mutation in a gene called the cystic fibrosis transmembrane conductance regulator (CFTR). • The CFTR gene is 180,000 base pairs long, and creates a protein which is 1,480 amino acids long • The CFTR protein provides a channel for chloride ions across membranes • Although most people without CF have two working copies of the CFTR gene, only one is needed to prevent cystic fibrosis. CF develops when neither gene works normally.
Loss of 3 nucleotides (TTT) results in the loss of phenylalanine at position 508 and creates a protein which does not fold normally and is degraded by the cell.
A defective CFTR will cause abnormal chloride ion transport, leading to abnormal concentrations of salt and water in cells. This results in a change of the normal osmotic pressure: less water than normal will be drawn into the lumen by osmosis, resulting in increased viscosity of the mucus in the airway
RESTRICTION ENZYMES A enzyme that cuts double-stranded DNA. The enzyme makes two incisions, one through each of the phosphate backbones of the double helix without damaging the bases. They were discovered in bacteria and are a defense mechanism.
RE #3 RE #2 RE #1 – + Electric current applied, fragments migrate down the gel by size—smaller ones move faster (and therefore go farther) than larger ones
Crime scene Suspect 1 Suspect 2 DNA collected 1 DNA amplified if necessary 2 DNA cut into fragments 3 DNA fragmentscompared 4 Figure 12.13
Fingernail clippings Victim Glove interior
PARENTAGE • A human egg cell and a human sperm cell both contain 23 single chromosomes • Fertilization brings these two sets of single chromosomes together to make 23 pairs of chromosomes in the embryo. • Each of these pairs of chromosomes contains genes inherited from the father and genes inherited from the mother, and these genes are in pairs, both coding for the same characteristic. • These different forms of the same gene • are called alleles.
mom dad 1 dad 2 1 2 3 4 5