Modern Concept of Genetics
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Modern Concept of Genetics

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  • 1. Modern Concept of Genetics Capsule Concept: Modern genetics has made great strides beyond the theories of classic Mendelian inheritance, especially in biochemistry. The modern investigator attempts to answer “how” and “why” questions using all of the tools of modern technology. The secrets of cell functions are contained in the biochemical events that take place in the cell nucleus and cytoplasm. Much scientific knowledge and technological skill has been applied to learn about the function of the cell’s organelles and its fine structure. In addition, modern geneticists devote investigative effort to the correction of general flaws by using techniques known as genetic engineering. Vocabulary: Cistron – a complete genetic code; a sequence of a DNA that provides code for a polypeptide chain. Double Helix – the shape of DNA Inducer – a small molecule that initiates the synthesis of mRNA Operator – that part of a nucleotide where mRNA synthesis begins Nucleotide – a compound consisting of a phosphate group linked to a 5-carbon sugar linked to a nitrogenous base Polyribosomes – a group of ribosomes that work together to build polypeptides Replication – the duplication of DNA Repressor – an inhibitor gene Sense Strand – that portion of DNA that is copied during mRNA synthesis Transcription – production of complementary strands of mRNA from DNA Translocation – the movement of a tRNA from one attachment site on one ribosome to another site during protein synthesis Triplet Codon – three nucleotides in a nucleic acid code unit Translation – the conversion of the genetic information carried by the tRNA molecule into the amino acid sequence of a polypeptide. Page 1
  • 2. NUCLEIC ACIDS AND PROTEIN SYNTHESIS The DNA Molecule Structure: The genetic material, located in the chromosomes, is a combination of nucleic acid and histones (short chained proteins). Deoxyribonucleic acid (DNA) is made up of units called nucleotides. Each nucleotide contains three components: the five – carbon sugar, a deoxyribose; a phosphate group; and a protein base. The protein base may be a double-ringed purine-adenine (A) or guanine (G) –a single- ringed pyrimidine-thymine (T) or cytosine (C). These four bases permit the formation of four different nucleotides. Each DNA molecule is composed of two strands of nucleotides. Study Figure 5.1. Notice that a phosphate group is joined to a sugar and the sugar to a protein base, forming a nucleotide. A nucleotide is linked with its complement through the protein bases. Figure 5.2 shows that the two strands of DNA resemble a ladder. The sugar –phosphate backbones form the sides of the ladder while the protein base pairs form the rungs of the ladder. The diagram shows that when nucleotides are joined together in a strand of DNA, the phosphate group attached to the 5’ (five prime) carbon of the sugar of one nucleotide links up with the 3’(three prime) carbon of the sugar in the adjacent nucleotide. This type of linkage in the sugar – phosphate backbone causes the sides of the DNA “ladder” to be uneven. The protein bases stick out to one side of the sugar –phosphate backbone. Fig 5.1 and 5.2 Page 2
  • 3. The protein bases of the nucleotides are joined together in a specific way. Adenine links only with thymine requiring two hydrogen bonds. Guanine will join only with cystine. This linkage requires three hydrogen bonds. In each DNA molecule, the number of adenine molecules always equals the numbers of thymines and the number of guanine molecules equals the number of cytosines. In 1962, James Watson and Francis Crick were awarded the Nobel Prize for working out the model of DNA structure. The DNA molecule is referred to as a double helix, two strands wound around each other. The two strands are antiparallel, extending in opposite directions. One has a 5’ phosphate group attachment at one end; the other has a 3’ attachment. The asymmetrical backbones cause the twisting with ten nucleotide pairs per turn. Figure 5.1 shows the Watson-crick model of DNA structure. In 1952, Rosalind Franklin showed through x-ray crystallography that DNA is a double helix. Using her work, Watson and Crick worked out the model that is now commonly accepted. Replication: Just before cell division begins, DNA makes an exact copy of itself. This process of DNA duplication is known as replication. The hydrogen bonds between the base pairs of the two nucleotide strands weaken and the two strands break apart. Each strand acts as a template forming a new nucleotide. This is accomplished by the action of two sets of enzymes: DNA helicase enzymes and DNA polymerase enzymes. The DNA helicase is working and where replication is taking place is known as the DNA fork. The polymerase enzyme helps the protein base in a given nucleotide to pick up and attach to a complementary base at the 3’ end. DNA is replicated in short segments known as Okazaki fragments. DNA ligase is the enzyme that joins these fragments together into a chromosome-length DNA molecule. Fig 5.3 Replication of DNA Page 3
  • 4. ABOUT RNA MOLECULES Ribonucleic acid (RNA) molecules are made of nucleotide subunits similar to those that are present in DNA. Like the nucleotides in DNA, each of the RNA nucleotides is made up of a phosphate group, a sugar, and a protein base. However, the sugar in RNA is ribose, a sugar that contains one more oxygen atom than the deoxyribose sugar contained in DNA. RNA differs from DNA in other ways also. RNA usually consists of a single strand of nucleotides, although it can form double-stranded sections. DNA is always double-stranded. The protein bases that compose RNA nucleotides are adenine, uracil, guanine and cytosine. RNA does not contain the amino acid thymine; adenine pairs with uracil instead. There are three kinds of RNA. Messenger RNA (mRNA) carries the code that specifies the sequence of amino acids in a polypeptide chain. The code carried by mRNA is copied from DNA; mRNA carries the genetic code for a protein from DNA to the ribosomes, where protein synthesis takes place. Transfer RNA (tRNA) ferries amino acids to the ribosomes and fits them into the correct place in the polypeptide chain. Each kind of amino acid is serviced by its own tRNA. Ribosomal (rRNA) is present in large quantities in the ribosomes, but its exact function is not known. DNA and TRANSCRIPTION As you have just read, specific pairing of the protein bases is the rule in double- stranded DNA. Adenine binds to thymine and guanine binds to cytosine. Each set of three nucleotides in linear sequence represents a code for an amino acid. This three nucleotide sequence is known as a triplet codon, or simply a codon. The entire amino acid sequ4ence in a protein is coded in a DNA molecule. The codon is the part of the genetic code that specifies a particular amino acid that is to be put into a polypeptide chain. DNA is not directly involved in protein synthesis. It serves as a template directing the production of messenger ribonucleic acid (mRNA). The production of the complementary single-stranded mRNA from DNA is called transcription. Messenger RNA carries to the ribosomes the code for the sequence of amino acids in the protein under construction. Transcription begins when that portion of a DNA molecule containing the code unwinds and is “recognized” by an enzyme known as RNA polymerase. The following series of events then occurs: RNA polymerase becomes attached to a linear group of nucleotides on DNA called the promoter. Then the two strands of DNA become separated and only one strand of DNA is copied. The strand of DNA that is copied is known as the sense strand. What determines the selection of a sense strand is unknown. RNA polymerase is a complex enzyme made up of several polypeptide chains. At least one chain recognizes and binds with the promoter site on the DNA sense, or coding, strand. Other sections of the enzyme move along the length of the DNA coding strand binding ribonucleotides (A, C, G, or U) to the lengthening RNA strand. When RNA polymerase reaches a specially coded portion of the DNA molecule, it stops transcribing mRNA and leaves the DNA. Page 4
  • 5. The RNA also detaches itself. (it is interesting to note the RNA polymerase works only in the 3’ to 5’ direction [upstream] on its DNA template and codes RNA [downstream] from the 5’ to 3’ direction.) The messenger RNA, which now contains the complementary code of its template DNA, moves out of the nucleus and becomes attached to a ribosome in the cytoplasm. PROTEIN SYNTHESIS Protein synthesis begins when mRNA becomes attached to a small subunit of the ribosome. The positioning of the mRNA on this ribosomal subunit is important. The first codon (AUG) on the mRNA must be positioned correctly in order for protein synthesis to begin. Meanwhile, individual amino acid molecules are activated by enzymes using energy from ATP. An AMP –amino acid- enzyme complex is formed: This complex is activated by transfer RNA (tRNA). Transfer RNA consists of a short chain of about 75 nucleotides arranged in a four-leaf clover configuration. Two segments of four-leaf clover are active. A third segment is composed of three protein bases which form an anticodon. The anticodon is attracted to its complementary codon on mRNA. The fourth segment of tRNA recognizes the amino acid complex and binds with the amino acid molecule. Now tRNA is ready to carry its specific amino acid molecule to the activated ribosome. The anticodon of tRNA binds to the AUG codon on mRNA> The amino acid carried by tRNA is methionine. At this point, the small ribosomal unit is a complex consisting of mRNA and its AUG codon, the anticodon of tRNA, and the amino acid, methionine. Next, a large ribosomal unit becomes attached to the complex. This large ribosomal unit has two binding sites fro tRNA known as peptidyl (P) site and an aminoacyl (A) site. Now the ribosome is in a condition to affect the building of a polypeptide chain. Now another tRNA with a complementary anticodon binds to the next codon in mRNA. Through the action of the enzyme peptidyl transferase the first amino acid and the second amino acid are joined by a peptide bond, leaving the first tRNA empty. Both amino acids are held by the second tRNA. The empty tRNA detaches from the ribosome and is now free to pick up more methionine. Next the ribosome moves along the mRNA in a process known as translocation. The second tRNA and mRNA are moved along the ribosome from the A site to the P site. By means of translocation, the third codon in mRNA is brought to the A site. The second codon is now at the P site. (The cycle of tRNA anticodon binding to its complementary codon on mRNA starts over again.) The complementary anticodon from an amino acid-bearing tRNA binds to the third mRNA codon. Peptidyl transferase caused peptide bond formation between the second and third amino acid. The second tRNA is now free, detaching from the ribosome. This process repeats until the ribosome reaches a stop codon. A special Page 5
  • 6. protein molecule known as Releasing Factor binds to the stop codon. This results in the detaching of mRNA from the ribosome. Then the ribosomal subunits separate. Now, the ribosome releases the newly formed polypeptide. Figure 5.4 four leaf clover configuration Figure 5.5 of tRNA Page 6