1. Classical Genetics

2. The Genome Contains The Entirety Of An Organism's Hereditary Information. If the DNA from a single (diploid) human cell were connected end-to-end and straightened, it would have a length of ~2 m and a width of ~2.4 nanometers Challenge In humans the entire stretch of DNA polymer is made of ~ 3·10 9 monomer units

3. IF YOU HAD A REALLY LONG STRING HOW WOULD YOU ORGANIZE IT? Question:

4. WHAT IF FROM TIME TO TIME YOU HAD TO ACCESS PART OF THE STRING? Another Question

5. The DNA is compacted into Chromosomes. highly condensed nuclear structures histone proteins

6. The DNA is compacted into Chromosomes. highly condensed nuclear structures histone proteins

7. Humans Have 23 Pairs of Chromosomes in (Diploid) Cells

8. Gene Gene is a stretch of DNA that contains the instructions for making a protein

9. With Better Understanding of Genomics, The Definition Of A Gene Has Changed DNA segment that encodes for a protein when and where it is made new definition of a Gene

10. This small subset of atoms provides an extensive molecular diversity 6 Atomic Constituents: C, H, N, O, P, S Build 99.6% Of All Living Matter

11. DNA, RNA: 4 nucleic bases Proteins: 20 amino acids 3 essential biomolecules for existence and continuation of life: variable units All life is based on complex structures (DNA, RNA, Proteins) which are made of these 6 elements

12. Adenine Guanine Thymine Cytosine 4 Nucleic Bases: Adenine (A), Thymine (T), Guanine (G), and Cytosine (C) Genetic code for DNA 2 strands of backbone locked by base pairs double helix

13. Adenine Guanine Thymine Cytosine 4 Nucleic Bases: Adenine (A), Thymine (T), Guanine (G), and Cytosine (C) Genetic code for DNA Pairing A-T G-C 2 strands of backbone locked by base pairs double helix

14. Hydrogen Bonding Helps Stabilize DNA H-bonding  attractive force between one electronegative atom (O,F, N) and a hydrogen covalently bonded to another electronegative atom.

15. Hydrogen Bonding Helps Stabilize DNA example: Kevlar derives part of its high strength from inter-molecular hydrogen bonds on neighboring polymer chains and aromatic (ring) stacking interactions between stacked strands

16. Nucleotide Pairing Is A Result of Hydrogen Bonding

17. The Structure of DNA Repetitive Structure Backbone Uniform Helix 0.34 nm

18. chemical variability nucleic bases in arbitrary sequence base -sequence encodes the meaning Notice that the widths of the pairs A-T and G-C are equal The Structure of DNA

19. Base compositions experimentally determined for a variety of organisms SpeciesA:TG:CA:G H. sapiens1.00 1.56 Salmon1.02 1.43 Wheat1.000.971.22 Yeast1.031.021.67 E. coli1.090.991.05 S. marcescens 0.950.860.70

20. Watson, Crick… Watson and Crick and Franklin

21. The structure of DNA: Notice that the widths of the pairs A-T and G-C are equal

22. The structure of DNA: Why is this significant ? chemical variability nucleic bases in arbitrary sequence Notice that the widths of the pairs A-T and G-C are equal base -sequence encodes the meaning Physically Repetitive, Chemically Variable repetitive structure repetitive structure backbone backbone uniform helix uniform helix

23. The structure of DNA: Physically Repetitive, Chemically Variable  Readability requires some sort of regular structure that can be algorithmically sifted through (semi-conservative replication)  Chemically variability in sequence provides a meaning and a genetic diversity Notice that the widths of the pairs A-T and G-C are equal chemical variability nucleic bases in arbitrary sequence base -sequence encodes the meaning repetitive structure repetitive structure backbone backbone uniform helix uniform helix

25. DNA Replication Is Semi-Conservative Provides opportunity for introduction and preservation of Novelty

26. semi-conservative replication of DNA

27. Cytosine 4 Nucleic Bases: Adenine (A), Uracil (U), Guanine (G), and Cytosine (C) Uracil Adenine Guanine Genetic code for RNA 1 strands of backbone with base pairs single helix Triplet of RNA bases (codon) translates into a particular amino acids

29. The Genetic Code Consists of Triplets of Bases Called Codons

30. The Order of Amino Acids Helps Determine the Shape of the Protein

31. Overview of What We’ve Discussed This AM: The structure of DNA: Shape governs the Function (Meaning)

32. The Hershey-Chase Experiments: What is the Hereditary Material Proteins or DNA? Use a Virus Let it infect a bacteria Radioactively label DNA & Proteins: 32 P-labeled DNA 35 S-labeled Protein

33. The Hershey-Chase Experiments: DNA is the Hereditary Material 32 P-labeled DNA 35 S-labeled Protein 2/3 within bacterium 1/4 within bacterium

35. 1) DNA encodes RNA 2) RNA encodes Proteins 3) Proteins encode shape/function  Genetic information (the MEANING) is encoded in the SEQUENCE of basis along the DNA strand;  DNA is not a direct template for protein synthesis; The Central Dogma of Molecular Biology: DNA  RNA  Protein

38. The History of Classical Genetics NATURE|Vol 441|25 May 2006

40. Classical Genetics NEW CORE CURRICULUM: FOUNDATIONS OF THE SCIENTIFIC PROCESS

41. 1) DNA encodes RNA 2) RNA encodes Proteins 3) Proteins encode shape/function Genetic information (the MEANING) is encoded in the SEQUENCE of basis along the DNA strand; DNA is not a direct template for protein synthesis; The Central Dogma of Molecular Biology: DNA  RNA  Protein

44. In the beginning… NATURE|Vol 441|25 May 2006 Mendel Johansen Morgan

45. 1941. Single Genes… Single Enzymes Johansen Beadle Tatum

46. 1944. Genes are Made of DNA Avery MacLeodMcCarty

47. 1953. Structure of DNA WatsonCrickWilkinsFranklin

48. 1977. Introns RobertsSharp

49. 1993. The first μRNA identified in C. elegans

50. Establishing Basic Terminology and Definitions: Gene = is a stretch of DNA that contains the instructions for making a protein; Allele = alternative forms of genes for a certain characteristics (ex. alleles for flower color or earlobe shape); Homozygous (EE, ee) & Heteorzygous (Ee); Genotype = genetic makeup of an organism; Phenotype = observed characteristics of organism; The phenotype is produced by the interaction of genes and the environment.

51. It has been long known that offspring resemble parents. Animals and plants selectively bred for many centuries. Gregor Mendel was the first to explain the principles of heredity in the mid-nineteenth century. He investigated heredity in pea plants Garden pea grow easily, produce large numbers of seeds quickly, and self-fertilize. Pea Plants have distinctive characters: Purple OR White flowers

52. Mendel isolated true-breeding strains Traits were selected because they had two distinct phenotypes Scientific Process of discovery….establishing Classical Genetics

53. Mendel crossbred plants with different alleles Gamete is a cell that is involved in sexual reproduction. A male and female gamete unite to produce a zygote that will develop into offspring.

54. Interpretation of Mendel’s Results  Laws of Heredity: Law of dominance: When an organism has 2 alleles for a given trait, the allele that is expressed (overshadows the expression of the other allele) is the dominant allele. The overshadowed allele is called recessive allele. notation convention: Y - dominant allele (ex. purple) y - recessive allele (ex. white) YY - homozygous dominant Yy - heterozygous yy - homozygous recessive

55. Deleterious recessive alleles persist in the population because heterozygous individuals carry the allele without developing the phenotype, and are not at a selective disadvantage. If both parents are homozygous for the recessive trait, all their progeny will usually also have the trait. Recessive traits are usually the result of a mutation causing loss or modification of gene product. ex. Albinism: characterized by the complete or partial absence of pigment in the skin, hair and eyes due to absence or defect of an enzyme involved in the production of melanin You could construct a family tree of either your family or friend’s family by using character for ear lobe type (recessive vs. dominant) non-attached is dominant

56. Co-Dominance Both alleles, when present, will contribute equally to the phenotype. Blood typing in humans- the ABO system; Rh factor incompatibility (erythrobalstosis feotalis). Terms: antigen, antibody, agglutination, Rh factor

57. Co-Dominance

59. Incomplete Dominance

60. Interpretation of Mendel’s Results  Laws of Heredity: Law of dominance: When an organism has 2 alleles for a given trait, the allele that is expressed (overshadows the expression of the other allele) is the dominant allele. The overshadowed allele is called recessive allele. Law of segregation: Parental alleles of a gene separate in process called meiosis into gametes (reproductive cells). In the process of gametes formation, the alleles that control a trait separate form one another retaining their individuality. Law of independent assortment: If two different genes are found on separate chromosomes, where the one allele goes is not influenced by where the other goes.

61. Law of Segregation

62. Law of Independent Assortment

63. parental alleles of a gene separate in process called meiosis into gametes semi-conservative replication of DNA

64. Next time…more about current efforts in Genetics