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

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

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

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

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

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

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

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

Take-Home Message: How is mRNA translated into protein? Translation converts protein-building information carried by mRNA into a polypeptide During initiation, an mRNA, an initiator tRNA, and two ribosome subunits join During elongation, amino acids are delivered to the complex by tRNAs in the order dictated by successive mRNA codons; the ribosome joins each to the end of the polypeptide chain Termination occurs when the ribosome reaches a stop codon in the mRNA; the mRNA and the polypeptide are released, and the ribosome disassembles

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

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

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

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

Mutations in the Beta Globin Gene

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

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

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

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

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

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

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

ANIMATED FIGURE: Sickle-cell anemia To play movie you must be in Slide Show Mode PC Users: Please wait for content to load, then click to play Mac Users: CLICK HERE

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

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

Take-Home Message: What happens after a gene becomes mutated? Mutations that result in an altered protein can have drastic consequences A base-pair substitution may change an amino acid in a protein, or shorten it by introducing a premature stop codon Frameshifts that occur after an insertion or deletion change an mRNA’s codon reading frame, so they garble its protein-building instructions

ANIMATED FIGURE: Base-pair substitution To play movie you must be in Slide Show Mode PC Users: Please wait for content to load, then click to play Mac Users: CLICK HERE

ANIMATION: Frameshift mutation To play movie you must be in Slide Show Mode PC Users: Please wait for content to load, then click to play Mac Users: CLICK HERE