Principles of Biology By Frank H. Osborne, Ph. D. Molecular Genetics Introduction •The topic of Molecular Genetics deals with the DNA of the cell and the process that is used to decode its genetic code and use the information to make proteins. •So, DNA contains the hereditary information that is passed from one generation to the next in humans. •The expression of DNA is protein. Introduction •The term given for making a protein is called "protein synthesis." This requires DNA to provide the coded genetic information, the three types of RNA, and the amino acids that are the components of the protein. •Protein synthesis is similar to making a car. The car is made of different parts brought together on the assembly line. Deoxyribonucleic Acid is DNA •DNA is a long polymer consisting of phosphate groups alternating with sugars. •Nucleotides are the subunits of nucleic acids. •A nucleotide consists of a base, a sugar and a phosphate. Deoxyribonucleic Acid is DNA •The sugar in DNA is called deoxyribose. •Each sugar has a base attached to it. The bases are made of carbon and nitrogen and are called nitrogenous bases. •There are two kinds of nitrogenous bases called purine bases and pyrimidine bases. •The purine bases found in DNA are adenine (A) and guanine (G). The pyrimidine bases found in DNA are cytosine (C) and thymine (T). Ribonucleic Acid is RNA •RNA is a long polymer consisting of phosphate groups alternating with sugars. The sugar in RNA is called ribose. •Each sugar has a base attached to it. •The purine bases found in RNA are adenine (A) and guanine (G). The pyrimidine bases found in RNA are cytosine (C) and uracil (U). •Both molecules are similar. DNA has deoxyribose and thymine, RNA has ribose and uracil. Structure of DNA •DNA has two strands, each with sugars alternating with phosphates, and with a base attached to each sugar. •The bases pair between the DNA strands. •Adenine always pairs with Thymine. If there is an Adenine on the first strand, there will be a Thymine opposite it. •Also, a Thymine on the first strand will be matched by an Adenine on the other. Structure of DNA •Similarly, Guanine pairs with Cytosine. •A Guanine on the first strand will be paired with a Cytosine on the other strand. Also, a Cytosine on the first strand will be paired with a Guanine on the other. •The base pairs of DNA are held together by weak attractions known as hydrogen bonds. Structure of DNA Replication of DNA •The two DNA strands unzip at the hydrogen bonds and each acts as a template. •The template is a pattern that will be replicated by enzymes synthesizing the new DNA strands. After the DNA strands are unzipped, the enzyme DNA-dependent DNA polymerase comes and makes a new strand matching each base with its correct partner. Replication of DNA •Wherever the template strand has an A, the new strand will receive a T; and wherever there is T, the new strand will receive an A. •Similarly, wherever the template strand has a G, the new strand will receive a C; and wherever there is a C, the new strand will receive a G. •As a result, the new strand will be an exact copy of the original strand. The process is called semiconservative replication. Gene Expression Protein Synthesis •The DNA causes a protein to be made as a result of a series of steps. •These steps are known as transcription and translation. Transcription •The DNA template is used to make messenger RNA (mRNA). The mRNA is the transcribed copy of the DNA molecule so it contains the genetic message encoded in the DNA. The mRNA travels to the endoplasmic reticulum where ribosomes attach to it. •The ribosomes decode the coded genetic message and translate it to make a protein molecule. The code that the mRNA contains was broken in the 1960s. Transcription •The genetic code is read from the mRNA molecule in units of three bases known as codons. In order to use the DNA code, look up the first base, then the second base, then the third base. For example if the codon is UUU, the amino acid is phe (phenylalanine). Translation •Translation of the coded message involves the ribosomes. Ribosomes are structures made of ribosomal RNA (rRNA) and protein molecules. • Each ribosome contains two components. The large component serves as the workspace where the protein is synthesized while the small component serves as the mechanism hat helps to join the amino acids together. Translation •Bringing the amino acids of the protein to the ribosome is the job of transfer RNA (tRNA). Each tRNA molecule carries a specific amino acid. •The system knows which one to use because the tRNA molecule has a specific anticodon that exactly matches the codon of the mRNA. So, if the mRNA codon was UUU, the anticodon would be AAA. Adenine and Uracil are complementary, so they would match exactly. Translation •As its tRNA brings each amino acid to the ribosome, the chain of amino acids grows in length by one amino acid. Enzymes on the ribosome remove the incoming amino acid from its tRNA and add it to the growing polypeptide chain using a condensation reaction. Mutations •Mutations are changes in genes. They can be transmitted to the offspring. •A point mutation results from the change in a single base in the DNA molecule. An example of a disease resulting from a point mutation is sicklecell anemia. •The hemoglobin molecule in sickle-cell patients differs in structure at only one place from the normal hemoglobin molecule. Mutations Frame-shift mutation •The code of the bases in DNA is translated to RNA. Transfer RNA decodes the mRNA molecule in groups of three. Each group of three is a reading frame. •Deletions of bases, duplications of bases, or other abnormalities can result in an alteration of the reading frame. Such an alteration is called a frame-shift mutation. Mutations Frame-shift mutation •Frame-shift mutations cause changes in the structures of proteins so that they will not function correctly. Problem 15 Revealed The Sequence of DNA - AAA G AT TA C C AT G G G C C G G C T - Problem 15 Revealed (a) Sequence of mRNA - AAA G AT TA C C AT G G G C C G G C T - U U U C U AA U G G U A C C C G G C C G A - Problem 15 Revealed (b) Sequence of Amino Acids - AAA G AT TA C C AT G G G C C G G C T - U U U C U AA U G G U A C C C G G C C G A - phe - leu - met - val - pro - gly - arg - Problem 15 Revealed (c) Misread transcription T - AAA G AT TA C C AT G G G C C G G C T A - U U U C U AA U G G U A C C C G G C C G A - phe - leu - met - val - pro - gly - arg his Problem 15 Revealed (d) Frameshift mutation - AAA G AT TA C C AT G G G C C G G C T - U U U C U AA U G G U A C C C G G C C G A - phe - leu - met - val - pro - gly - arg - ser - asn - gly - thr gly - arg - The End Principles of Biology Molecular Genetics