Human Genetics

1. Human Genetics Concepts and Applications Eighth Edition Powerpoint Lecture Outline Ricki Lewis Prepared by Dubear Kroening University of Wisconsin-Fox Valley

2. Chapter 10 Gene Action: From DNA to Protein

3. 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

4. Central Dogma Figure 10.1

5. Two Types of Nucleic Acids Table 10.2

6. Major Types of RNA Table 10.3

7. mRNA • Carries information from DNA to ribosome • Produced in the nucleus • Transported to the ribosome • A three nucleotide codon specifies a particular amino acid

8. 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

9. tRNA • Cloverleaf shape • Anticodon of tRNA forms hydrogen bonds with the mRNA codon and has a specific amino acid at the other end Figure 10.5

10. Figure 10.6

11. Protein Synthesis • Transcription • production of mRNA in the nucleus • mRNA processing • an mRNA exits the nucleus • Translation • Production of amino acid chain within ribosome

12. 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

13. 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

14. Figure 10.2

15. Base Pairing Template DNA strand C C T A G C T A C G G A U C G A U G mRNA strand G G A T C G A T G Coding DNA strand

16. Steps in Transcription • Proteins and RNA polymerase bind to promoter region Figure 10.7

17. Transcription Initiation RNA polymerase reads the nucleotides on the template strand from 3’ to 5’ and creates an RNA molecule that looks like the coding strand Figure 10.8

18. 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

19. 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

20. RNA Processing Figure 10.10

21. Translation • The process of reading the RNA sequence of an mRNA and creating the amino acid sequence of a protein • Occurs within the ribosome Figure 10.11

22. The Genetic Code • Codons are thetriplet 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

23. 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!

24. The Genetic Code Table 10.5

25. 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

26. Translation Initiation Figure 10.13

27. Translation Elongation Figure 10.14a

28. Elongation Figure 10.14b

29. Elongation Figure 10.14c

30. Termination Figure 10.15

31. Translation: Multiple Copies of a Protein Are Made Simultaneously Figure 10.16

32. 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

33. Levels of Protein Structure Figure 10.17

34. Misfolded Proteins Are Destroyed • Ubiquitin tags misfolded proteins • Transports it to a proteasome Figure 10.19

35. Misfolding of ProteinImpairs 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

36. Prions • Protein folding disorder  Infectious prions cause scrapie (sheep), bovine spongiform encephalopathy (cows), and a variant Creutzfeldt-Jakob disease (humans) Figure 10.20