Genetics: The Old and the New (and there is a “Lot” of Newness)

1. Genetics: The Old and the New (and there is a “Lot” of Newness) • Introduction • Analogy to an “information broker” • Radical transformation of the science (i.e., what is a revolution in the sciences) • Genetics of inheritance - Mendelian genetics (> 1860) • Genetics of cell’s operation - molecular genetics (> 1950) • The “Genetic Code” • Genetics “on the cutting edge”: last five years

3. Introduction • Why is an “information broker” important in living systems? • What constitutes a “revolution” in the sciences?

4. The Old: Genetics of Inheritance (1860’s) • Classical or Mendelian genetics (Gregory Mendel) • Competing hypotheses • Blended inheritance versus particulate inheritance • Testing the hypotheses (Scientific Method!!) • Flower color in peas (1 parent with red flowers and 2nd parent with white flowers) • Results: two classes of flowers • Red (300 seedlings) • White (100 seedlings) • Pink (0 seedlings) • Conclusion • Hypothesis: Data support the particulate theory Data reject blended theory • Specific quantitative data: 3:1 ratio (strange but revealing quantitative ratio!) 300 100

5. Rules of Classical Mendelian Genetics (1860’s) • Traits passed from parent to offspring consistent with particulate inheritance model • Mechanism unknown at the time (now we know) • Two “copies” of each trait in each individual (3:1 ratio) • One from each parent • Some “copies” are dominant and some copies are recessive • Dominant traits = expressed • Recessive traits = expressed only if both copies recessive

6. Mendelian Genetics (1860’s) and Coming Forward • Gene - trait determined by a sequence of DNA • Allele - alternative forms (“copies”) of the same gene (e.g., normal hemoglobin vs sickle cell hemoglobin; blue vs brown eyes) • No longer called “copies” but alleles!!! • Dominant allele (e.g., brown eyes) • Recessive allele (e.g., blue eyes) • Chromosomes - physical packaging of genes in nucleus • Pairs of chromosomes • Genome - all of the genes of an organism in the nucleus • Humans: ~20,000 genes

7. Question If you were to cross rabbits that were black with rabbits that were white and the offspring were gray, this outcome would supportthe theory of ___________. A particulate inheritance B conspicuous inheritance C Lamarckian inheritance D blended inheritance E None of the above

8. Question The “unit of inheritance” documented by Mendel is now called the ___. A hybrid B parental strain C gene D dominant allele E the “Mendel”

9. Question In genetic crosses the re-current quantitative ratio of 3:1 among offspring supports the presence of ____ copy/copies of each gene in an organism of all species of eukaryotes. A four B three C two D one

10. Genes and Chromosomes

11. DNA to Genes to Chromosomes Gene

12. Chromosomes, Genes and Alleles Sickle Cell Normal Normal Hemoglobin Chemistry Normal Attached Attached Ear Lobe Free Free Blue Brown Eye Color: Brown Blue Blue A O Blood Group B O Individual One (Thee) Individual Two (Me)

13. Genetics of Humans: Sex Determination • Humans = 46 chromosomes or 23 pairs • Sex determination on one pair of chromosomes (Pair No. 21) • X and Y chromosome • Female: two “X” chromosomes • Male: one “X” and one “Y” chromosome • Female produces only X chromosome eggs • Male produces both X and Y chromosome sperm • Who determines the sex of offspring? • Sex-linked traits … examples?

14. 46 chromosomes in each human (23 pairs) ~20,000 different genes in each human Only ~1.5% of genome active … we think (stay tuned!) Millions of nucleotide differences between any two people Complexity of the Human Genome Affymetrix

15. Genetics: The Old and the New • Introduction • Analogy to an “information broker” • Radical transformation of the science (i.e., revolution) • Genetics of inheritance - Mendelian genetics (> 1860) • Genetics of cell’s operation - molecular genetics (> 1950) • The “Genetic Code” • Genetics “on the cutting edge” (> 2005)

16. Molecular Genetics • Structure of DNA and RNA - information storage, transmission and expression • Replication of the information - copying/duplication • Transcription of the information - transcribing • Translation of the information - expressing as proteins (requires new language with new alphabet!)

17. Watson and Crick: a Revolution in the Sciences 1953 Double helix Contribution of Watson and Crick: Monomer = Nucleotides (A, T, C and G) Polymer = polynucleotide (nucleic acid) 3 D Structure of Nucleic Acid = DNA Double Helix Watson Crick

18. Nucleotides: The Building Blocks of Nucleic Acids • Nucleotide: three components • Sugar • DNA: deoxyribose • RNA: ribose • Phosphate group • Base (N=4) • Adenine (A) • Guanine (G) • Cytosine (C) • Thymine (T)

19. DNA Structure • Join nucleotides • Alternating phosphate and sugar • DNA • 2 strands of nucleotides • Joined by nitrogen base pairs (A, T, C and G) • Bonding pattern (fidelity!) • Adenine : Thymine • Cytosine : Guanine • Information broker - “biological alphabet” (A,T,C and G)

20. Question Nucleic acids such as DNA and RNA are polymers (macromolecules) of the monomers called ____. A amino acids B monosaccharides C nucleotides D lipids

21. Question While the English alphabet contains 26 letters, the biological alphabet of the DNA is based on whopping number of ___ nucleotides/”letters”. A 2 B 4 C 6 D 8

22. Question The term “fidelity” in base pairing of nucleotides in DNA means that the nucleotide thymine always pairs with nucleotide ___. A europocil B cytosine C another thymine D guanine E adenine

23. Genetics: The Old and the New (and there is a “Lot” of Newness) • Introduction • Analogy to an “information broker” • Radical transformation of the science (i.e., what is a revolution in the sciences) • Genetics of inheritance - Mendelian genetics (> 1860) • Genetics of cell’s operation - molecular genetics (> 1950) • The “Genetic Code” • Genetics “on the cutting edge”: last five years

24. Molecular Genetics: General Theme

25. Molecular Genetics: Structure of DNA and RNA • DNA - Deoxyribonucleic acid (nucleus; double strand) • RNA - Ribonucleic acid (protoplasm; single strand) • Monomer - nucleotides (N = 4 in DNA) • Guanine (always binds to Cytosine - G:C) • Adenine (always binds to Thymine - A:T) • Cytosine (always binds to Guanine - C:G) • Thymine (always binds to Adenine - A:T) • Polymer - polynucleotide (DNA & RNA)

26. Sequence of Nucleotides and Genes • Linear sequences of nucleotides • Gene: sequence of nucleotides responsible for a specific trait (e.g., eye color; hemoglobin; attached ear lobes, carbon metabolism, sickle cell anemia, enzyme) • Remember the iphone image Number of nucleotides 431 1150 1225 653 1580 102 954

27. Molecular Genetics: A Single Gene • Exact sequence of nucleotides is important • Any change in sequence changes the information (“RAT to CAT”) and constitutes a mutation • Daily: you experience 10,000’s of mutations but all are corrected (for the most part) A T T A G C G G T A T G C C G G T T A A G A T C C G A T T A G C G G T A CG C C G G T T A A G A T C C G

28. Molecular Genetics: General Theme Replication

29. Molecular Genetics: Replication • Replication: process of duplicating DNA to produce a new and exact copy with fidelity • includes “spell checking”

30. Molecular Genetics Replication

31. Molecular Genetics: Transcription • Information in DNA “transcribed” into another type of message - mRNA (messenger RNA) • Analogue to transcribing spoken into written language • mRNA made in nucleus and subsequently shuttled to protoplasm • In protoplasm, mRNA to the ribosome (protein synthesis)

32. Compartmentation: Ribosome Figure 23.22 23-494

33. Molecular Genetics: Translation in the Ribosome Replication

34. Molecular Genetics: Translation • Information in mRNA “translated” into polypeptide and then functional protein (new language and “new letters of the alphabet”!) • Monomer: amino acids • Location: ribosome for protein synthesis • Genetic code: specificity and fidelity • All organisms and all species use the exact same process • Example: genetically modified organisms (GMO’s)

35. Protein Synthesis and Genetic Code • One gene codes for one protein • Protein drives chemical process in cell (e.g., enzymes) • Original source of information = DNA • Intermediate source of information = RNA • All living things on Earth use the absolute same genetic code

36. Transcription, Translation and Protein Assembly http://www.youtube.com/watch?v=983lhh20rGY

37. Question In the following figure, the process linking the DNA to RNA (see white arrow) is called _______. A replication B transcription C translation D gene splicing

38. Question Making a copy of DNA is called ___. A replication B transcription C translation D. photocopying

39. Question The sum of all information contained in your DNA and copied in each cell in your body is called your ___. A gene base B gene traits C genome D. genetic material

40. Mutations and DNA Repair • Mutations • Change in sequence of nucleotides in DNA • Causes of mutations • Oxygen (e.g., aging) • Nuclear radiation • X-rays • UV light (e.g., beach time!) • Higher elevations (e.g., mountain tops, airplanes) • DNA Repair • 10,000 ‘hits’ per day (you and me!!) • Cells repair damage - excision and repair process • BUT …. repair not equal in all individuals

41. Molecular Genetics: A Single Gene (Single Strand) • Exact sequence of nucleotides is important • Any change in sequence changes the information (“RAT to CAT”) and constitutes a mutation • Excision and repair A T T A G C G G T A T G C C G G T T A A G A T C C G A T T A G C G G T A CG C C G G T T A A G A T C C G

42. Genetics: The Old and the New • Introduction • Information broker • Radical transformation of the science (i.e., revolution) • Genetics of inheritance - Mendelian genetics (> 1860) • Genetics of cell’s operation - molecular genetics (> 1950) • The “Genetic Code” • Genetics “on the cutting edge” (last five years)

43. Genetics “on the Cutting Edge” • Genetic counseling (probability of offspring with particular traits) • Forensic sciences (e.g., CSI TV series) • Genetic engineering : GMO’s (Genetically Modified Organisms) • Genetic “Sleuthing” • Human applications (e.g., ice man in the Alps + 5,000 years) • Genetic basis of autism • Genetics, mutations and cancer (next week’s lecture) • Editing of genes

44. Genetic Counseling

45. Genetic Counseling using “Gene Chips”

46. Forensic Sciences

47. Genetics “on the Cutting Edge” • Genetic counseling (probability of offspring with particular traits) • Forensic sciences (e.g., CSI TV series) • Genetic engineering (e.g., “starlight” strain of corn) • GMO’s (Genetically Modified Organisms) • Genetic “Sleuthing” • Human applications (e.g., ice man in the Alps + 5,000 years) • Genetic basis of autism • Genetics, mutations and cancer (next week’s lecture) • Editing of genes

49. Genetics: The Old and the New (and there is a “Lot” of Newness) • Introduction • Analogy to an “information broker” • Radical transformation of the science (i.e., what is a revolution in the sciences) • Genetics of inheritance - Mendelian genetics (> 1860) • Genetics of cell’s operation - molecular genetics (> 1950) • The “Genetic Code” • Genetics “on the cutting edge”: last five years