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Dna (deoxyribonucleic acid) structure and functions

  1. 1. DNA (Deoxyribonucleic acid) Structure and Functions Namrata Chhabra M.D.Biochemistry 1
  2. 2. 2
  3. 3. An international team of researchers from UK, Germany, and China discovered the oldest ancestor of man 3
  4. 4. Researchers have deciphered the information of ancient DNA extracted from the thigh bone of an early human who died 400,000 years ago in Spain. Researchers say DNA strands of 400,000-year-old early human can help build clearer picture of human family tree. 4
  5. 5. Oldest Human DNA Reveals Mysterious Branch of Humanity An artist's impression of the early humans that are estimated to have lived 400,000 years ago. 5
  6. 6. 6
  7. 7. DNA passes on genetic information through its chemical structure and molecular behavior. A simple fertilized egg becomes a complex human being of forty trillion cells. 7
  8. 8. DNA- the molecular basis of inheritance ● DNA is a molecule that contains the information an organism requires to develop, live and reproduce. ● These ‘instructions’ are found inside every cell and are transferred from parents to their children. 8
  9. 9. Learning objectives ● To conceptualize the key structural features of DNA, and ● apply the learned concepts in illustrating the functions of DNA 9
  10. 10. DNA ● A Storehouse of genetic information. ● found in chromosomes, mitochondria and chloroplasts 10
  11. 11. The DNA structure is probably the most iconic of all biomolecules. It has inspired the architects to design the staircases, decorations, pedestrian bridges (as in Singapore, and more. The Helix Bridge, Singapore, at night. 11
  12. 12. History of DNA Structure discovery ● Until the 1950s, the structure of DNA remained a mystery. ● The double-helical structure of DNA was discovered through the work of James Watson, Francis Crick, Rosalind Franklin, and other researchers. 12
  13. 13. 13
  14. 14. Double helical structure of DNA By Bdna.gif: Spiffistanderivative work: Jahobr (talk) - Bdna.gif, Public Domain, In the model, the orange and red atoms mark the phosphates of the sugar-phosphate backbones, while the blue atoms on the interior of the helix belong to the nitrogenous bases. 14
  15. 15. 15
  16. 16. DNA structure DNA is composed of subunits called nucleotides A nucleotide is made up of a sugar (deoxyribose), a phosphate group, and one of four nitrogenous bases: adenine (A), thymine (T), guanine (G) or cytosine (C). 16
  17. 17. Ribose and deoxyribose 17
  18. 18. Bases present in DNA 18
  19. 19. Pyrimidines 19
  20. 20. Purines 20
  21. 21. Nucleosides and Nucleotides 21
  22. 22. Vote 22
  23. 23. Vote 23
  24. 24. N-Glycosidic linkage 24
  25. 25. Anti and syn configuration in glycosidic bonds 25
  26. 26. Primary structure of DNA ● A linear sequence of deoxyribonucleotides linked together by 3'-5' phosphodiester linkages ● The informational content of DNA resides in the sequence in which monomers—purine and pyrimidine deoxyribonucleotides— are ordered 26
  27. 27. Primary structure of DNA ● The polymer possesses a polarity; one end has a 5'-hydroxyl or phosphate terminal while the other has a 3'-phosphate or hydroxyl terminal. ● Traditionally, a DNA sequence is drawn from 5’ to 3’ end. 27
  28. 28. What makes DNA an acid ? 28
  29. 29. Watson and Crick's model of DNA The structure of DNA, as represented in Watson and Crick's model, is a double-stranded, antiparallel, right-handed helix. The sugar-phosphate backbones of the DNA strands make up the outside of the helix, while the nitrogenous bases are found on the inside and form hydrogen-bonded pairs that hold the DNA strands together. 29
  30. 30. Anti-parallel strands of DNA ● The two strands of the double-helical molecule, each of which possesses a polarity, are antiparallel; ie, one strand runs in the 5' to 3' direction and the other in the 3' to 5' direction. ● Sugar-phosphate chains wrap around the periphery. 30
  31. 31. Sugar-Phosphate backbone DNA nucleotides are linked by covalent bonds, formed between the deoxyribose sugar of one nucleotide and the phosphate group of the subsequent. This arrangement makes an alternating chain of deoxyribose sugar and phosphate groups in the DNA polymer, a structure known as the sugar-phosphate backbone 31
  32. 32. Bases in DNA ● Bases (A,T, C and G) occupy the core, forming complementary A · T and G · C Watson-Crick base pairs. ● The DNA double helix is held together mainly by- Hydrogen bonds. ● Two hydrogen bonds between A:T pairs while three hydrogen bonds between C: G pairs. 32
  33. 33. Hydrogen bonds Sharing of a hydrogen atom covalently attached to an electronegative element (typically O-H and N-H groups) between a lone pair of electrons on another electronegative element. ● The electronegative atom with the lone pair electrons is called the Hydrogen Bond Acceptor ● The electronegative atom bonded to the hydrogen is called the Hydrogen Bond Donor ● The Hydrogen Bond Donor must be aligned 180 degrees to the Hydrogen Bond Acceptor 33
  34. 34. Vote 34
  35. 35. Each pair of bases lies flat, forming a "rung" on the ladder of the DNA molecule. The bases in DNA are planar and have a tendency to "stack". Major stacking forces: hydrophobic interaction and Vander Waals forces. The Bases in DNA 35
  36. 36. Right handed helix In Watson and Crick's model, the two strands of DNA twist around each other to form a right-handed helix. As one looks down the double helix, the base residues form a spiral in a clockwise direction. 36
  37. 37. Chargaff’s rules Erwin Chargaff was an Austro-Hungarian Biochemist who was a professor of Biochemistry at Columbia University medical school. Chargaff discovered two rules that helped to the discovery of the double helix structure of DNA. 37
  38. 38. Chargaff’s rules ● The first rule was that in DNA the number of guanine units is equal to the number of cytosine units, and the number of adenine units is equal to the number of thymine units. This hinted at the base pair makeup of DNA. ● The second rule was that the relative amounts of guanine, cytosine, adenine and thymine bases vary from one species to another. This hinted that DNA rather than protein could be the genetic material. 38
  39. 39. The impact of double stranded structure of DNA Template strand - In the double-stranded DNA molecules, the genetic information resides in the sequence of nucleotides on one strand, the template strand. This is the strand of DNA that is copied during ribonucleic acid (RNA) synthesis. It is sometimes referred to as the noncoding strand. Coding strand- The opposite strand is considered the coding strand because it matches the sequence of the RNA transcript (but containing uracil in place of thymine) that encodes the protein. 39
  40. 40. Major and Minor grooves ● Major and minor grooves wind along the DNA molecule parallel to the phosphodiester backbones. ● In these grooves, proteins can interact specifically with exposed atoms of the nucleotides (via specific hydrophobic and ionic interactions) without disrupting the base pairing of the double-helical DNA molecule. 40
  41. 41. Forms of DNA Property A-DNA B-DNA Z-DNA Helix Handedness Right Right Left Base Pairs per turn 11 10.4 12 Rise per base pair along axis 0.23nm 0.34nm 0.38nm Pitch 2.46nm 3.40nm 4.56nm Diameter 2.55nm 2.37nm 1.84nm Conformation of Glycosidic bond anti anti Alternating anti and syn Major Groove Present Present Absent Minor Groove Present Present Deep cleft 41
  42. 42. Forms of DNA 42
  43. 43. Physiological form of DNA- B DNA ● The horizontal arrow indicates the width of the double helix (20 Å). ● The vertical arrow indicates the distance spanned by one complete turn of the double helix (34 Å). ● The major and minor grooves are depicted. ● Hydrogen bonds between A/T and G/C bases indicated by short horizontal lines. 43
  44. 44. How long is our DNA ? ● If you stretched the DNA in one cell all the way out, it would be about 2m long. ● All the DNA in all our cells put together would be about twice the diameter of the Solar System. 44
  45. 45. Amazing facts ● There are about 3 billion nucleotides in human DNA. ● The average length of a human nucleotide is 0.6 nanometers, or 0.0000000006 meters, so human DNA is about 1.8 meters (5 feet) long. ● The 5 feet of DNA is being packed into each cell in our body, and the average diameter of the a nucleus in a human cell is only 10 microns, or 0.00001 meters. Clearly, DNA is packaged (twisted, wrapped and folded) so that it is very compact. ● There are about 50 to 75 trillion cells in a human body, so if the DNA from each cell were placed end to end, the chain would be from 90 to 135 trillion meters long. 45
  46. 46. Prokaryotic versus Eukaryotic DNA 46
  47. 47. Prokaryotic versus Eukaryotic DNA ● EuKaryotic cells contain a very large quantity of DNA (human cells have at least a thousand times more DNA than a typical bacteria cell). ● E.coli chromosomes have about 4.7 x 106 base pairs which results in a length of 1.6 mm. ● An E.coli cell, however is only 0.002 mm long . ● That explains why the DNA must be folded in order to fit into the cell. 47
  48. 48. Tertiary structure of DNA In eukaryotic cells, DNA is folded into chromatin. Chromatin consists of very long double-stranded DNA molecules and a nearly equal mass of rather small basic proteins termed histones as well as a smaller amount of nonhistone proteins (most of which are acidic and larger than histones) and a small quantity of RNA. 48
  49. 49. Levels of organization of DNA ● Nucleosomes are composed of DNA wound around a collection of histone molecules. ● The disk-like nucleosome structure has a 10-nm diameter and a height of 5 nm. ● The 10-nm fibril consists of nucleosomes arranged with their edges separated by a small distance (30 bp of DNA) with their flat faces parallel with the fibril axis. 49
  50. 50. Levels of organization of DNA ● The 10-nm fibril is probably further supercoiled with six or seven nucleosomes per turn to form the 30-nm chromatin fiber. ● In interphase chromosomes, chromatin fibers appear to be organized into 30,000–100,000 bp loops or domains anchored in a scaffolding (or supporting matrix) within the nucleus. 50
  51. 51. Chromosomes ● At metaphase, mammalian chromosomes possess a twofold symmetry, with the identical duplicated sister chromatids connected at a centromere, the relative position of which is characteristic for a given chromosome. ● The 3 x 109 base pairs of DNA in humans are organized into the haploid complement of 23 chromosomes. ● 51
  52. 52. Functions of DNA 1. DNA Replication It provides the information inherited by daughter cells or offspring. 52
  53. 53. Functions of DNA 2. Storehouse of genetic code The DNA holds the information for all the proteins to be created for the cell. The bases are grouped in triplets called codons that code for a specific amino acid. The whole genetic code stores the information for all cell types to reproduce. 53
  54. 54. Functions of DNA 3. Mutation and Recombination ● During DNA replication, different DNA segments can be spliced through gene linkage. ● The process can create new combinations of traits in offspring. ● If the protein helps the species survive, it may evolve over time. ● However, some mutations may be non-beneficial or lethal. 54
  55. 55. Human evolution 55
  56. 56. Functions of DNA 4.Gene expression ● Each cell contains a full set of genes. ● Cells from different tissues and organs appear and function differently. ● The reason is that only some of the DNA of each cell is used to make proteins. 56
  57. 57. Summary 57
  58. 58. Summary DNA consists of four bases—A, G, C, and T—that are held in linear array by phosphodiester bonds through the 3' and 5' positions of adjacent deoxyribose moieties. DNA is organized into two strands by the pairing of bases A to T and G to C on complementary strands. These strands form a double helix around a central axis. 58
  59. 59. Summary The 3 x 109 base pairs of DNA in humans are organized into the haploid complement of 23 chromosomes. DNA provides a template for its own replication and thus maintenance of the genotype and for the transcription of the roughly 30,000 human genes into a variety of RNA molecules. 59
  60. 60. Key references 1. Harper’s illustrated Biochemistry 31st edition. 2. Lehninger principles of Biochemistry 7the edition 3. Lippincott Illustrated Review Biochemistry, 5th edition. 4. 60
  62. 62. Thank you 62