1. LECTURE 04: CHROMOSOMAL BASIS OF INHERITANCE I Fhow do we know that genes are parts of chromosomes? Fhow are they arranged on chromosomes? Fare chromosomes only genes? Fhow is chromosome number maintained through the generations?

2. LECTURE 04: CHROMOSOMAL BASIS OF INHERITANCE I Fwhat is the chromosomal basis for Mendel’s 1st law - equal segregation? Fwhat is the chromosomal basis for Mendel’s 2nd law - independent assortment? Fhow does all the DNA fit into a tiny nucleus?

3. LECTURE 04: CHROMOSOMAL BASIS OF INHERITANCE I FCH3 key concepts Fhistorical development of the chromosome theory... genetics + cell biology Fchromosomes Fmitosis & meiosis Fchromosome behavior & inheritance patterns Forganelle chromosomes

4. CHAPTER 3: KEY CONCEPTS F genes are parts of chromosomes F mitosis = 1 nuclear division  2 daughter nuclei identical to original nucleus F meiosis = 2 nuclear divisions  4 genetically distinct daughter nuclei with one set of chromosomes F Mendel’s laws of (1) equal segregation & (2) independent assortment are based on (1) separation of each member of a chromosome pair & (2) the independent movement of chromosome pairs

5. CHAPTER 3: KEY CONCEPTS F chromosomes can be identified microscopically using various visible landmarks F a chromosome (chromatid) contains a single DNA molecule F DNA winds around protein spools, spooled units then coil, loop & supercoil to form a chromosome F much of eukaryotic DNA is present in multiple copies F most multiple copy DNA has no known function

6. OVERVIEW

7. GENETICS + CELL BIOLOGY F mechanisms of character transmission (so far studied) unknown until chromosomes were accessible by more advanced microscopy F behavior of Mendel’s particles parallel chromosome movement – merger of cytology and genetics – Sutton-Boveri Theory (1902)

8. GENETICS + CELL BIOLOGY F cell biology findings leading to understanding of remarkable correlation with transmission: F nuclear divisions – initially ‘aberrations’ in cell physiology F 2 gametes fusion during fertilization F discovery of chromosomes F discovery that somatic chromosome # constant for given species; # did not seem to correlate with species complexity ( e.g., ant with 1pr) F chromosomes present in pairs* – diploid number F gametes formed have half as many – haploid number F each member of diploid pair are derived from each parent; each parent contributes a haploid complement to zygote

9. GENETICS + CELL BIOLOGY F Sutton-Boveri theory: genes are located on chromosomes F Mendelian genes and observed chromosomes... F occur in pairs F segregate equally into gametes F assort independently into gametes F evidence is convincing... but correlative only...

10. GENETICS + CELL BIOLOGY F Sutton-Boveri theory: genes are located on chromosomes F problems? F do chromosomes retain their physical integrity through interphase? F some chromosome pairs look the same... how can you tell that they assort independently?

11. CHROMOSOME THEORY - SEX LINKAGE Fa grasshopper sp. has unpaired & heteromorphic pair Fobserved 2 patterns with = frequency (counted) Fnon-homologous chromosomes assort independently F... but not random... mechnanism?

12. CHROMOSOME THEORY - SEX LINKAGE Fa thistle sp. has 12 chromosome pairs F12 variants identified Feach variant had a 3rd copy of one chromosome Fchromosomes all carry genetically distinct material

13. CHROMOSOME THEORY - SEX LINKAGE Fmeiosis in a beetle Tenebrio Fsegregation of heteromorphic chromosomes X and Y in  Fgametes receive different material F  s don’t have Y

14. CHROMOSOME THEORY - SEX LINKAGE Fchromosome complement in 2 insect spp. Fgender correlates with 2 patterns, s have 2 X s, no Y F  s have 1 X and either 0 or 1 Y

15. CHROMOSOME THEORY - SEX LINKAGE F X and Y segregate like homologues in  s F  s make 2 kinds of gametes in equal proportions Fresponsible for determination of gender

16. CHROMOSOME THEORY - SEX LINKAGE F in some species... F  are heterogametic WZ F  are homogametic ZZ F distinguish system from XY F found in some birds, reptiles, fish, and some insects (moths and butterflies) F same rules apply as in XY but in reverse

17. CHROMOSOME THEORY - SEX LINKAGE Fcompare this pattern with X -linked inheritance in flies (discussed in lecture 03)

18. CHROMOSOME THEORY - SEX LINKAGE Fcompare this pattern with X -linked inheritance in flies (discussed in lecture 03)

19. CHROMOSOME THEORY - SEGREGATION

20. F in flies...  X :autosome ratio  1,  mRNA on    X :autosome rato < 1,  mRNA on   F XXY =   X 0 =   fertility is determined by Y,  X 0 = sterile  Fin humans... Fgender determined by Y

21. CHROMOSOME THEORY - SEGREGATION Fsometimes observe “exceptional” progeny

22. CHROMOSOME THEORY - SEGREGATION F proof of (... ok, strong evidence for) the chromosomal theory of inheritance

23. CHROMOSOME THEORY F 2 important points to remember... F not all genes on sex chromosomes have to do with gender or sexual differentiation F many autosomal genes are important for gender

24. CHROMOSOMES F levels of genetic organization: 1. ploidy – chromosome sets 2. n – how many of each type 3. size – arbitrary / relative 4. centromere – position 5. landmarks – chromomeres, puffs, abnormalities 2 n = 6

25. CHROMOSOMES text order of ideas for this section of chapter 3 very small DNA very large genome medium chromosome topography small chromosome structure  my order of ideas for this section of chapter 3 very small DNA very large genome medium chromosome topography small chromosome structure 

26. CHROMOSOMES - n n

27. CHROMOSOMES - CENTROMERE Falso... (d) acentric and (e) dicentric... later!

28. CHROMOSOMES - n, SIZE, CENTROMERE

30. CHROMOSOMES - TOPOGRAPHY Fhuman nucleus, metaphase, n = 23 Fcentromeres - note positions Fchromomeres - bead-like thickenings

31. CHROMOSOMES - TOPOGRAPHY Ftomato nucleus, prophase I, n = 12 Fcentromeres - orange Fheterochromatin - green: dense, note position... later Feuchromatin - white: less dense, active genes... later

32. CHROMOSOMES - TOPOGRAPHY F Drosophila melanogaster chromosomes, n = 4 Fheterochromatin - blue: dense, note position... later Feuchromatin - gold: less dense, active genes... later

33. CHROMOSOMES - TOPOGRAPHY Fmouse nucleus, satelite DNA, different G+C content Fmultiple tandem DNA sequence repeats Fmuch of it in centromeric heterochromatic regions

34. CHROMOSOMES - TOPOGRAPHY F tomato chromosome- 2 F nucleoli: F nuclear organelles F containing rRNA F 1 or more / nucleus (spp.) F nucleolar organizers (NO): F genes encoding rRNA F redundant - high copy

35. CHROMOSOMES - TOPOGRAPHY F telomeres F no visible “structure” F FISH (fluorescent in situ hybridization) F telomere-specific DNA F tandem arrays of non-coding sequence F overcomes replication problem... more on this later

36. CHROMOSOMES - TOPOGRAPHY Fhuman nucleus, metaphase, n = 23, Giemsa stain Fbanding patterns - consistent, chromosome-specific FG-dark & G-light... significance of bands?

37. CHROMOSOMES - TOPOGRAPHY F Drosophila chromosomes F centromeres F telomeres F euchromatin F heterochromatin F polytene chromosomes F chromocenter

38. CHROMOSOMES - TOPOGRAPHY why is this significant?

39. F Zea maize, n = 10

40. CHROMOSOMES - GENES

41. F single gene ID with FISH

42. CHROMOSOMES - GENES F meaningful relationships ?

43. CHROMOSOMES - GENES F meaningful relationships ?

44. CHROMOSOMES - GENES F repetative genes - duplication ?

45. CHROMOSOMES - STRUCTURE F honeybee metaphase chromosomes F continuous “fiber” 30 nm wide

46. CHROMOSOMES - STRUCTURE F D. melanogaster DNA molecule from 1 chromosome* F single continuous “fiber” 15 mm (5 x longer than the fly!) F a chromosome contains only 1 DNA molecule

47. CHROMOSOMES - STRUCTURE

48. 1.nucleosome (10 nm) 2.solonoid (30 nm)

49. CHROMOSOMES - STRUCTURE 3.scaffold loop (? nm) 4.supercoil (chromatid)

50. CHROMOSOMES - STRUCTURE F where should the genes be ?

51. TUTORIAL #1: T.9.19 or R.9.21 F go to the TUTORIAL page on the genetics web site F download the file tut1-06F.pdf F follow instructions and attempt as many of the problems as possible F you will continue to work on these in tutorial #1, with the assistance of your TA and your peers