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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Powerpoint Lecture Outline Human Genetics Concepts and Applications Eighth Edition Ricki Lewis Prepared by Dubear Kroening University of Wisconsin-Fox Valley 10-1 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chapter 10 Gene Action: From DNA to Protein 10-2 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Gene Expression • Production of protein from the instructions on the DNA • Proteins have diverse functions in the body examples are listed in Table 10.1 • Protein synthesis requires several steps including: Transcription - production of mRNA RNA processing Translation - production of protein using mRNA, tRNA, and rRNA 10-3 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Central Dogma Figure 10.1 10-4 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Two Types of Nucleic Acids Table 10.2 10-5 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Major Types of RNA Table 10.3 10-6 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. mRNA • Carries information from DNA to ribosome • Produced in the nucleus • Transported to the ribosome • A three nucleotide codon specifies a particular amino acid 10-7 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. rRNA • With associated proteins make up ribosome • Two subunits that join during protein synthesis • Provides structural support and some are a catalyst (ribozymes) Figure 10.4 10-8 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. tRNA • Cloverleaf shape • Anticodon of tRNA forms hydrogen bonds with the mRNA codon and has a specific amino acid at the Figure 10.5 other end 10-9 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Figure 10.6 10-10 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Protein Synthesis • Transcription – production of mRNA in the nucleus • mRNA processing – an mRNA exits the nucleus • Translation – Production of amino acid chain within ribosome 10-11 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Transcription • RNA is the bridge from DNA to protein • mRNA is synthesized from the template strand of DNA • The complementary strand is the coding strand of DNA • Requires enzyme RNA polymerase and transcription factors 10-12 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Transcription Factors • In bacteria, operons control gene expression • In more complex organisms transcription factors control gene expression and link genome to environment • Over 2,000 • Mutations in transcription factors may cause a wide range of effects 10-13 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Figure 10.2 10-14 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Base Pairing Template DNA strand C G C G T A A U G C C G T A A U C G T C G A T G mRNA strand G G A Coding DNA strand 10-15 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Steps in Transcription Figure 10.7 • Proteins and RNA polymerase bind to promoter region 10-16 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Transcription Initiation Figure 10.8 RNA polymerase reads the nucleotides on the template strand from 3’ to 5’ and creates an RNA molecule that looks like the coding strand 10-17 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Transcription Occurs in three steps: • Initiation promoter • Elongation RNA polymerase adds nucleotides to growing RNA • Termination Sequences in the DNA prompt the RNA polymerase to fall off, ending the transcript 10-18 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. RNA Processing • mRNA transcripts are modified before use as a template for translation: • Addition of capping nucleotide at the 5’ end • Addition of polyA tail to 3’ end • Important for moving transcript out of nucleus and for regulating when translation occurs • Splicing occurs, removing internal sequences Introns are sequences removed Exons are sequences remaining 10-19 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. RNA Processing Figure 10.10 10-20 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Translation • The process of reading the RNA sequence of an mRNA and creating the amino acid sequence of a protein Figure 10.11 • Occurs within the ribosome 10-21 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. The Genetic Code • Codons are the triplet code groups of three RNA nucleotides used to encode one amino acid • The genetic code refers to which codons encode which amino acids, one start codon, and three stop codons • Non overlapping • Genetic code is universal evidence of a common ancestor • The genetic code is degenerate some codons encode the same amino acid 10-22 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. mRNA Nucleotides and the Amino Acids in a Protein • Proteins are formed from 20 amino acids in humans Codons of three nucleotides: AAA AGA ACA AUA AAG AGG ACG AUG AAC AGC ACC AUC AAU AGU ACU AUU GAA GGA GCA GUA GAG GGG GCG GUG GAC GGC GCC GUC GAU GGU GCU GUU CAA CGA CCA CUA CAG CGG CCG CUG CAC CGC CCC CUC CAU CGU CCU CUU UAA UGA UCA UUA UAG UGG UCG UUG UAC UGC UCC UUC UAU UGU UCU UUU Allows for 64 potential codons => sufficient! 10-23 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. The Genetic Code Table 10.5 10-24 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Translation Composed of three steps • Initiation – Translation begins at start codon (AUG = methionine) • Elongation – The ribosome uses the tRNA anticodon to match codons to amino acids and adds those amino acids to the growing peptide chain • Termination – Translation ends at the stop codon – UAA, UAG or UGA 10-25 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Translation Initiation Figure 10.13 10-26 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Translation Elongation Figure 10.14a 10-27 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Elongation Figure 10.14b 10-28 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Elongation Figure 10.14c 10-29 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Termination Figure 10.15 10-30 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Translation: Multiple Copies of a Protein Are Made Simultaneously Figure 10.16 10-31 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Protein Folding • After synthesis, proteins must be folded into three-dimensional shape • Enzymes and chaperone proteins assist • Misfolded proteins are tagged and dismantled • Proteins can fold in more than one way • Misfolded proteins can cause disease 10-32 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Levels of Protein Structure Figure 10.17 10-33 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Misfolded Proteins Are Destroyed •Ubiquitin tags misfolded proteins •Transports it to a proteasome Figure 10.19 10-34 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Misfolding of Protein Impairs Function • Misfolded prion protein disrupts functions of other normally folded prion proteins • Aberrant conformation can be passed on, propagating like an “infectious” agent Table 10.6 10-35 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Study guide- DNA- Ch. 9; RNA & protein synthesis- Ch. 10.1-10.2 • History of DNA knowledge: – Discoveries – Who isMiescher Garrod Frederick Griffith Avery, Macleod, McCarty Chargaff Hershey & Chase Levene Wilkins & Franklin Watson & Crick Meselson & Stahl 10-36 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Prions • Protein folding disorder Infectious prions cause scrapie (sheep), bovine spongiform encephalopathy (cows), and a variant Creutzfeldt-Jakob disease (humans) Figure 10.20 10-37 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Experiments of transforming factor– Griffith experiment – Hershey & Chase bacteriophage experiment • DNA structure– – – – – Components of nucleotide Directionality 5’, 3’ Arrangement of components Bonding • DNA replication – – – – Model- semiconservative ProcessEnzymes- helicase, DNA polymerase- function Complementary base pairing rules 10-38 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • What are chromosomes? • Central Dogma of Biology • RNA components – 3 Types of RNA – Complementary base rules • Protein Synthesis– Transcription- process , where it occurs – Translation- process, where it occurs – Enzymes involved- RNA polymerase and transcription factors. • Triplet code, codon, anticodon, amino acid, proteins. • Folding of proteins • Mutations 10-39