lecture 7 Nucleic Acids.pdf
- 1. Nucleic Acids • Genetic information is encoded by molecules named nucleic acids because they were originally isolated from the nucleus of eukaryotic cells • There are two related types of nucleic acid, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) • The master copy of each cell’s genome is stored on long molecules of DNA, which may each contain many thousands of genes • Each gene is thus a linear segment of a long DNA molecule • In contrast, RNA molecules are much shorter, are used to transmit the genetic information to the cell machinery, and carry only one or a few genes • Certain viruses use RNA to encode their genomes as well as transmitting genetic information to the cell machinery • These RNA viruses have short genomes, rarely more than a dozen genes, as opposed to the hundreds or thousands of genes carried on the DNA genomes of cells
- 2. Chemical Structure of Nucleic Acids • DNA and RNA are linear polymers made of subunits known as nucleotides • The information in each gene is determined by the order of the different nucleotides, just as the information in this sentence is due to the order of the 26 possible letters of the alphabet • There are four different nucleotides in each type of nucleic acid and their order determines the genetic information • Each nucleotide has three components: a phosphate group, a five-carbon sugar, and a nitrogen-containing base • The phosphate groups and the sugars form the backbone of each strand of DNA or RNA • The bases are joined to the sugars and stick out sideways • In DNA, the sugar is always deoxyribose; whereas, in RNA, it is ribose • Both sugars are pentoses, or five-carbon sugars. Deoxyribose has one less oxygen than ribose • It is this chemical difference that gave rise to the names deoxyribonucleic acid and ribonucleic acid • Both sugars have five-membered rings consisting of four carbon atoms and an oxygen
- 3. Chemical Structure of Nucleic Acids • The fifth carbon forms a side chain to the ring • The five carbon atoms of the sugar are numbered 1´, 2´, 3´, 4´ and 5´ • By convention, in nucleic acids, numbers with prime marks refer to the sugars and numbers without prime marks refer to the positions around the rings of the bases • Nucleotides are joined by linking the phosphate on the 5´carbon of the (deoxy) ribose of one nucleotide to the 3´-position of the next as shown below • The phosphate group is joined to the sugar on either side by ester linkages, and the overall structure is therefore a phosphodiester linkage • The phosphate group linking the sugars has a negative charge
- 4. Nucleotide
- 6. DNA and RNA Bases • There are five different types of nitrogenous bases associated with nucleotides • DNA contains the bases adenine, guanine, cytosine and thymine • These are often abbreviated to A, G, C and T, respectively. RNA contains A, G and C, but T is replaced by uracil (U) • From the viewpoint of genetic information, T in DNA and U in RNA are equivalent • The bases found in nucleic acids are of two types, pyrimidines and purines • The smaller pyrimidine bases contain a single ring whereas the purines have a fused double ring • Adenine and guanine are purines;and thymine, uracil and cytosine are pyrimidines
- 9. Nucleosides and Nucleotides • A base plus a sugar is known as a nucleoside • A base plus a sugar plus phosphate is known as a nucleotide • One may distinguish between deoxynucleosides or deoxynucleotides where the sugar is deoxyribose, and ribonucleosides or ribonucleotides that contain ribose • The names of the nucleosides are similar to the names of the corresponding bases • The nucleotides do not have names of their own but are referred to as phosphate derivatives of the corresponding nucleoside • For example, the nucleotide of adenine is adenosine monophosphate, or AMP • Three-letter abbreviations for the bases such as ade, gua, etc., are sometimes used when writing biochemical pathways or for the names of genes involved in nucleotide metabolism • When writing the sequence of a nucleic acid, the single letter abbreviations are used (A, T, G and C for DNA or A, U, G and C for RNA) • The letter N is often used to refer to an unspecified base
- 10. Double Stranded DNA Forms a Double Helix • A strand of nucleic acid may be represented in various ways, either in full or abbreviated to illustrate the linkages • As remarked above, nucleotides are linked by joining the 5´ phosphate of one to the 3´-hydroxyl group of the next • Typically, there is a free phosphate group at the 5´-end of the chain and a free hydroxyl group at the 3´-end of a nucleic acid strand • Consequently, a strand of nucleic acid has polarity and it matters in which direction the bases are read off • The 5´-end is regarded as the beginning of a DNA or RNA strand • This is because genetic information is read starting at the 5´-end • RNA is normally found as a single-stranded molecule, whereas DNA is double stranded • Note that the two strands of a DNA molecule are antiparallel, as they point in opposite directions
- 11. Double Stranded DNA Forms a Double Helix • This means that the 5´-end of one strand is opposite the 3´-end of the other strand • Not only is DNA double-stranded, but the two separate strands are wound around each other in a helical arrangement • This is the famous double helix first proposed by Francis Crick and James Watson in 1953 • The DNA double helix is stabilized both by hydrogen bonds between the bases and by stacking of the aromatic rings of the bases in the center of the helix • DNA forms a right-handed double helix • To tell a right-handed helix from a left handed helix, the observer must look down the helix axis (in either direction) • In a right-handed helix, each strand turns clockwise as it moves away from the observer (in a left-handed helix it would turn counterclockwise)
- 13. Base Pairs are Held Together by Hydrogen Bonds • In double stranded DNA, the bases on each strand protrude into the center of the double helix where they are paired with the bases in the other strand by means of hydrogen bonds • Adenine (A) in one strand is always paired with thymine (T) in the other, and guanine (G) is always paired with cytosine (C) • Consequently, the number of adenines in DNA is equal to the number of thymines, and similarly the numbers of guanine and cytosine are equal • Note that the nucleic acid bases have amino or oxygen side-groups attached to the ring • It is these chemical groups, along with the nitrogen atoms that are part of the rings themselves, that allow the formation of hydrogen bonds • The hydrogen bonding in DNA base pairs involves either oxygen or nitrogen as the atoms that carry the hydrogen, giving three alternative arrangements: O– H–O, N–H–N and O–H–N.
- 14. Base Pairs are Held Together by Hydrogen Bonds • Each base pair consists of one larger purine base paired with a smaller pyrimidine base • So, although the bases themselves differ in size, all of the allowed base pairs are the same width, providing for a uniform width of the helix • The A-T base pair has two hydrogen bonds and the G-C base pair is held together by three bonds • Before the hydrogen bonds form and the bases pair off, the shared hydrogen atom is found attached to one or the other of the two bases (shown by the complete lines in • During base pairing, this hydrogen also bonds to an atom of the second base (shown by the dashed lines) • Although RNA is normally single-stranded, many RNA molecules fold up, giving double-stranded regions • In addition, a strand of RNA may be found paired with one of DNA under some circumstances • Furthermore, the genome of certain viruses consists of double-stranded RNA • In all of these cases, the uracil in RNA will base pair with adenine • Thus the base-pairing properties of the uracil found in RNA are identical to those of the thymine of DNA
- 15. Complementary Strands Reveal the Secret of Heredity • If one of the bases in a base pair of double stranded DNA is known, then the other can be deduced. If one strand has an A, then the other will have a T, and vice versa • Similarly, G is always paired with C. This is termed complementary base pairing • The significance is that if the base sequence of either one of the strands of a DNA molecule is known, the sequence of the other strand can be deduced • Such mutually deducible sequences are known as complementary sequences • It is this complementary nature of a DNA double helix that allows genetic information to be inherited • Upon cell division, each daughter cell must receive a copy of the parental genome • This requires accurate duplication or replication of the DNA • This is achieved by separating the two strands of DNA and using omplementary base pairing to make a new partner for each original strand