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Chapter 9 From DNA to Protein

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1 Chapter 9 From DNA to Protein

2 9.1 The Aptly Acronymed RIPs
A tiny amount of ricin, a natural protein found in castor-oil seeds, can kill an adult human – there is no antidote Ricin is a ribosome-inactivating protein (RIP Other RIPs include shiga toxin, made by Shigella dysenteriae bacteria, and enterotoxins made by E. coli bacteria, including the strain O157:H7

3 Some RIPs Figure 9.1 A few ribosome-inactivating proteins. The structure of RIPs are strikingly similar. One of their polypeptide chains (red) helps the molecule cross a cell’s plasma membrane. The other chain (orange) destroys the cell’s capacity for protein synthesis.

4 9.2 DNA, RNA, and Gene Expression
Transcription converts information in a gene to RNA DNA → transcription → mRNA Translation converts information in an mRNA to protein mRNA → translation → protein

5 The Nature of Genetic Information
Each DNA strand consists of a chain of four kinds of nucleotides: adenine (A), thymine (T), guanine (G), and cytosine (C) The sequence of the bases in the strand is the genetic code Genes

6 Converting a Gene to an RNA
Transcription DNA is transcribed to RNA Most RNA is single stranded RNA uses uracil in place of thymine RNA uses ribose in place of deoxyribose

7 A DNA Nucleotide base (guanine) 3 phosphate groups sugar (deoxyribose)
Figure 9.2 Comparing nucleotides of DNA and RNA. sugar (deoxyribose) A DNA nucleotide: guanine (G), or deoxyguanosine triphosphate

8 An RNA Nucleotide base (guanine) 3 phosphate groups sugar (ribose)
Figure 9.2 Comparing nucleotides of DNA and RNA. sugar (ribose) An RNA nucleotide: guanine (G), or guanosine triphosphate

9 deoxyribonucleic acid RNA ribonucleic acid adenine A adenine A
DNA deoxyribonucleic acid RNA ribonucleic acid adenine A adenine A sugar– phosphate backbone guanine G guanine G cytosine C cytosine C nucleotide base Figure 9.3 DNA and RNA compared. base pair thymine T uracil U DNA has one function: It permanently stores a cell’s genetic information, which is passed to offspring. RNAs have various functions. Some serve as disposable copies of DNA’s genetic message; others are catalytic. Still others have roles in gene control. Nucleotide bases of DNA Nucleotide bases of DNA Figure 9-3 p151

10 RNA in Protein Synthesis
Messenger RNA (mRNA) Contains information transcribed from DNA Ribosomal RNA (rRNA) Main component of ribosomes, where polypeptide chains are built Transfer RNA (tRNA) Delivers amino acids to ribosomes

11 Converting mRNA to Protein
Translation mRNA is translated to protein

12 Gene Expression A cell’s DNA sequence (genes) contains all the information needed to make the molecules of life Gene expression A multistep process including transcription and translation Gene -> trait

13

14 9.3 Transcription: DNA to RNA
RNA polymerase A new RNA strand is complementary

15 DNA Replication and Transcription
In transcription Uracil (U) nucleotides pair with A nucleotides RNA polymerase adds nucleotides to the transcript

16 The Process of Transcription
Promoter (site in DNA close to the start of a gene)

17 RNA polymerase binds to a promoter in the DNA
RNA polymerase binds to a promoter in the DNA. The binding positions the polymerase near a gene. In most cases, the base sequence of the gene occurs on only one of the two DNA strands. Only the DNA strand complementary to the gene sequence will be translated into RNA. promoter sequence in DNA gene region RNA polymerase 1 2 The polymerase begins to move along the DNA and unwind it. As it does, it links RNA nucleotides into a strand of RNA in the order specified by the base sequence of the DNA. The DNA winds up again after the polymerase passes. The structure of the “opened” DNA at the transcription site is called a transcription bubble, after its appearance. DNA unwinding DNA winding up RNA 3 Zooming in on the gene region, we can see that RNA polymerase covalently bonds successive nucleotides into an RNA strand. The base sequence of the new RNA strand is complementary to the base sequence of its DNA template strand, so it is an RNA copy of the gene. direction of transcription Figure 9.4 Animated Transcription. By this process, a strand of RNA is assembled from nucleotides according to a template: a gene region in DNA. Figure It Out: After the guanine, what is the next nucleotide that will be added to this growing strand of RNA? Stepped Art Figure 9-4 p152

18 RNA transcripts DNA molecule
Figure 9.5 Typically, many RNA polymerases simultaneously transcribe the same gene, producing a structure often called a “Christmas tree” after its shape. Here, three genes next to one another on the same chromosome are being transcribed. Figure It Out: Are the polymerases transcribing this DNA molecule moving from left to right or from right to left? Figure 9-5 p153

19 Post-Transcriptional Modifications
In eukaryotes, RNA is modified before it leaves the nucleus as a mature mRNA Introns Nucleotide sequences that are removed from a new RNA Exons Sequences that stay in the RNA

20 Example Introns and Exons:
JUSTICESCALIAEUDIFKFNDI88ADMITS2DHFJDHEDOESNOTFEELSKFJKDCJDIFLQULIFIEDTORULEKDKFNDOINFHTEEDHFJDFHUDWONTHEACCURACYOFTHISSCIENCE Exons only (Introns removed) JUSTICESCALIAADMITSHEDOESNOTFEELQUALIFIEDTORULEONTHEACCURACYOFTHISSCIENCE

21 Alternative Splicing Alternative splicing

22 gene promoter exon intron exon intron exon DNA transcription exon
new transcript RNA processing Figure 9.6 Animated Post-transcriptional modification of RNA. Introns are removed and exons spliced together. Messenger RNAs also get a poly-A tail and modified guanine “cap.” exon exon exon 5′ 3′ finished RNA cap poly-A tail Figure 9-6 p153

23 9.4 RNA and the Genetic Code
Base triplets in an mRNA encode a protein-building message Ribosomal RNA (rRNA) and transfer RNA (tRNA) translate that message into a protien

24 mRNA – The Messenger mRNA carries protein-building information to ribosomes Codon

25 three nucleotide bases. In the large chart, the left column lists a
codon’s first base, the top row lists the second, and the right column lists the third. Sixty-one of the triplets encode amino acids; the remaining three are signals that stop translation. The amino acid names that correspond to abbreviations in the chart are listed above. Figure It Out: Which codons specify the amino acid lysine (lys)? Figure 9-7a p154

26 Genetic Code Genetic code Consists of 64 mRNA codons (triplets)
Twenty kinds of amino acids are found in proteins Some amino acids can be coded by more than one codon Some codons signal the start or end of a gene AUG (methionine) is a start codon UAA, UAG, and UGA are stop codons

27 three nucleotide bases. In the large chart, the left column lists a
codon’s first base, the top row lists the second, and the right column lists the third. Sixty-one of the triplets encode amino acids; the remaining three are signals that stop translation. The amino acid names that correspond to abbreviations in the chart are listed above. Figure It Out: Which codons specify the amino acid lysine (lys)? Figure 9-7b p154

28 From DNA to RNA to Amino Acids
a gene region in DNA transcription codon codon codon mRNA Figure 9.8 Example of the correspondence between DNA, RNA, and proteins. A DNA strand is transcribed into mRNA, and the codons of the mRNA specify a chain of amino acids. translation methionine (met) tyrosine (tyr) serine (ser) amino acid sequence

29 rRNA and tRNA – The Translators
tRNAs deliver amino acids to ribosomes tRNA has an anticodon complementary to an mRNA codon, and a binding site for the amino acid specified by that codon Ribosomes, which link amino acids into polypeptide chains, consist of two subunits of rRNA and proteins

30 amino acid attachment site
tRNA Structure anticodon anticodon amino acid attachment site Figure 9.10 tRNA structure.

31 Translation: Ribosome and tRNA
Figure 9.10 tRNA structure.

32 9.5 Translation: RNA to Protein
Translation converts genetic information carried by an mRNA into a new polypeptide chain The order of the codons in the mRNA determines the order of the amino acids in the polypeptide chain

33 Translation Translation occurs in the cytoplasm of cells
Translation occurs in three stages: Initiation Elongation Termination

34 Initiation An initiation complex is formed
A small ribosomal subunit binds to mRNA The anticodon of initiator tRNA base-pairs with the start codon (AUG) of mRNA A large ribosomal subunit joins the small ribosomal subunit

35 Elongation The ribosome assembles a polypeptide chain as it moves along the mRNA Initiator tRNA carries methionine, the first amino acid of the chain The ribosome joins each amino acid to the polypeptide chain with a peptide bond

36 Termination When the ribosome encounters a stop codon, polypeptide synthesis ends Release factors bind to the ribosome Enzymes detach the mRNA and polypeptide chain from the ribosome

37 1 Ribosome subunits and an initiator tRNA converge on an mRNA. A second tRNA binds to the second codon. first amino acid of polypeptide start codon (AUG) initiator tRNA A peptide bond forms between the first two amino acids. peptide bond 2 The first tRNA is released and the ribosome moves to the next codon. A third tRNA binds to the third codon. 3 A peptide bond forms between the second and third amino acids. 4 A peptide bond forms between the third and fourth amino acids. The process repeats until the ribosome encounters a stop codon in the mRNA. 6 The second tRNA is released and the ribosome moves to the next codon. A fourth tRNA binds the fourth codon. 5 Figure 9.11 Animated Translation. Translation initiates when ribosomal subunits and an initiator tRNA converge on an mRNA. tRNAs deliver amino acids in the order dictated by successive codons in the mRNA. The ribosome links the amino acids together as it moves along the mRNA, so a polypeptide forms and elongates. Translation terminates when the ribosome reaches a stop codon. Stepped Art Figure 9-11 p156

38 Transcription polysomes ribosome subunits tRNA Convergence of RNAs
mRNA Figure 9.12 Animated Overview of translation. Translation polypeptide Figure 9-12a p157

39 Practice The DNA base sequence of the gene coding for a short polypeptide is T A C G C T A G G C G A T T G A C T Transcribe this DNA. Translate into the amino acid sequence.

40 Polysomes Many ribosomes may simultaneously translate the same mRNA, forming polysomes mRNA polysomes newly forming polypeptide

41 9.6 Mutated Genes and Their Protein Products
If the nucleotide sequence of a gene changes, it may result in an altered gene product, with harmful effects Mutations Small-scale changes in the nucleotide sequence of a cell’s DNA that alter the genetic code

42 Mutations and Proteins
A mutation that changes a UCU codon to UCC is “silent” – it has no effect on the gene’s product because both codons specify the same amino acid Other mutations may change an amino acid in a protein, or result in a premature stop codon that shortens it – both can have severe consequences for the organism

43 Common Mutations Base-pair-substitution
May result in a premature stop codon or a different amino acid in a protein product Example: sickle-cell anemia Deletion or insertion Can cause the reading frame of mRNA codons to shift, changing the genetic message Example: thalassemia

44 Hemoglobin and Anemia Hemoglobin is a protein that binds oxygen in the lungs and carries it to cells throughout the body The hemoglobin molecule consists of four polypeptides (globins) folded around iron-containing hemes – oxygen molecules bind to the iron atoms Defects in polypeptide chains can cause anemia, in which a person’s blood is deficient in red blood cells or in hemoglobin

45 Mutations in the Beta Globin Gene

46 A Hemoglobin, an oxygen-binding protein in red blood cells
A Hemoglobin, an oxygen-binding protein in red blood cells. This pro-tein consists of four polypeptides: two alpha globins (blue) and two beta globins (green). Each globin has a pocket that cradles a heme (red). Oxygen molecules bind to the iron atom at the center of each heme. Figure 9-13a p158

47 B Part of the DNA (blue), mRNA (brown), and amino acid sequence (green) of human beta globin. Numbers indicate the position of the base pair in the coding sequence of the mRNA. Figure 9-13b p158

48 C A base-pair substitution replaces a thymine with an adenine
C A base-pair substitution replaces a thymine with an adenine. When the altered mRNA is translated, valine replaces glutamic acid as the sixth amino acid of the polypeptide. Hemoglobin with this form of beta globin is called HbS , or sickle hemoglobin. Figure 9-13c p158

49 D A deletion of one base pair causes the reading frame for the rest of the mRNA to shift, so a different protein product forms. This frameshift results in a defective beta globin chain. The outcome is beta thalassemia, a genetic disorder in which a person has an abnormally low amount of hemoglobin. Figure 9-13d p158

50 E An insertion of one base pair causes the reading frame for the rest of the mRNA to shift, so a different protein product forms. This frameshift results in a defective beta globin chain. The outcome is beta thalassemia. Figure 9-13e p158

51 Sickle-Cell Anemia Sickle-cell anemia is caused by a base-pair substitution which produces a beta globin molecule in which the sixth amino acid is valine instead of glutamic acid (sickle hemoglobin, HbS) HbS molecules stick together and form clumps – red blood cells become distorted into a sickle shape, and clog blood vessels, disrupting blood circulation throughout the body Over time, sickling damages organs and causes death

52 sickled cell glutamic acid valine normal cell
Figure 9.14 Animated Sickle-cell anemia. Figure 9-14 p159

53 Thalassemia and Frameshifts
Another type of anemia, beta thalassemia, is caused by the deletion of the twentieth base pair in the beta globin gene Deletions cause a frameshift, in which the reading frame of the mRNA codons shifts Frameshifts garble the genetic message, just as incorrectly grouping a series of letters garbles the meaning of a sentence

54 Thalassemia and Transposable Elements
Beta thalassemia can also be caused by insertion mutations, which also cause frameshifts Insertion mutations are often caused by the activity of transposable elements, which are segments of DNA that can insert themselves anywhere in a chromosome


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