1. Classical Papers in Genetics Olga Russakovsky 10 / 28 / 04 CS 374

2. Outline Sulton, W. S. The Chromosomes in Heredity, 1903 Demerec, M. What is a Gene? 1933 Crick, Francis. Central Dogma of Molecular Biology, 1970.

3. 1903

4. The Chromosomes in Heredity Background: Mendel’s experiments Cell organization and division Which chromosomes? Roles of chromosomes Alleles and dominance

5. Mendel’s experiments Peas 1:2:1 genotypic ratios, 3:1 phenotypic Mendel’s brilliant conclusion: “while in the organism maternal and paternal potentialities are present in the field of each character, the germ cells in respect to each character are pure.” Deviations from Mendel correspond to deviations in chromosome processes

6. Cell organization and division Bateson quote “It is impossible to be presented with the fact that in Mendelian cases the crossbred produces on an average equal numbers of gametes of each kind, that is to say, a symmetrical result, without suspecting that this fact must correspond with some symmetrical figure of distribution of the gametes in the cell division by which they are produced.”

7. Cell organization and division Relationships between chromosomes and genes in Brachystola 1) Prophase – two equivalent chromosome series (maternal and paternal) B C B C A A

8. Cell organization and division Chromosomes and genes 2) Metaphase (synapsis) – union of pairs of the homologues BCBCAA

9. Cell organization and division Chromosomes and genes 3) Meiosis II – first postsynaptic division equational, so no differentiation BCBCAA BCBCAA

10. Cell organization and division Chromosomes and genes 4) Meiosis I (reducing division) – separation of homologous chromosomes B C B C A A BC B C A A

11. Cell organization and division Chromosomes and genes 5) Chromosomes retain individuality throughout cell cycle B C B C A A BC B C A A

12. Which chromosomes? Do all maternal chromosomes go to one pole, and paternal to the other? Probably not B C B C A A BC B C A A versus

13. Which chromosomes? If maternal and paternal separated, 1) No crossbreeding can produce more variety than first cross Consider AB x AB  ABAB parent cell  ½ AB and ½ AB germ cells Then crossbreeding yields germ cells: AB ½ AB AB  ½ AB and ½ AB

14. Which chromosomes? If maternal and paternal separated, 2) Only 4 different combinations in offsprings of a single pair Consider AB x CD  ¼ AC, ¼ AD ¼ BC, ¼ BD ABCD ABABCDCD AC, AD, BC, BD

15. Which chromosomes? If maternal and paternal separated, 3) Can receive traits from only one grandparent each from the paternal and maternal lines ABCD ABABCDCD AC, AD, BC, BD

16. Which chromosomes? More careful research Matter of chance, paternal or maternal ABCD 16 different possible germ cells: ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD Only 2 possible combinations X 2 unrelated individuals: 256 possible offsprings!

17. Which chromosomes? So for humans, with 16 chromosomes minimum: 8 homologous pairs, so 2 8, or 256, combinations of germ cells, so (2 8 ) 2, or some huge number, of possible children

18. Which chromosomes? This “serves to bring the chromosome theory into final relation with the known fact of heredity; for Mendel himself followed out the actual combinations of two and three distinctive characters and found them to be inherited independently of one another and to present a great variety of combinations in the second generation.”

19. Roles of chromosomes Numbers can’t confirm roles Studies of larvae lacking certain chromosomes Confirmed relationship between characters and chromosomes Studies of Brachystola confirmed law of segregation of characters

20. Roles of chromosomes Similarities between germ-cell division and heredity: Purity of units Independent transmission So half of offsprings contain each trait Evidence and experiments  double basis for each character, even in pure- breeding forms, because of pairs of homologues

21. Alleles and Dominance Definite relationship between allelomorphs, or unit characters, and chromosomes Entire chromosome or only part is an allele? Think about variety! At least some must carry multiple alleles (i.e. multiple genes)

22. Alleles and Dominance Chromosome entirely dominant, or divided into parts? Greatly increases variety, yet also greatly increases complexity of research Breakthrough: sometimes observed correlation between traits Explanation: same chromosome, sometimes both traits dominant over homologue, sometimes only one dominant

23. Alleles and Dominance Chromosome 1: AB Chromosome 2: ab Offsprings: observed correlation between traits Chromosome 1: Ab Chromosome 2: aB Offsprings: no observed correlation (opposite correlation, actually) Key:A = green color of seed a = brown color of seed B = big leaves b = small leaves

24. 1933

25. What is a gene? Gene definition analyzed Stability of the gene Nature of gene changes Role of genes

26. Gene definition Gene: a minute organic particle capable of reproduction located in a chromosome responsible for the transmission of a hereditary characteristic Goal: to see how this definition can be extended

27. Gene definition Size of gene Determine volume of chromosomes, approximate number of genes, and divide one by the other Proposed upper limits: 10, 20, 50, 60, 70 millimicrons About a few organic molecules genes

28. Gene definition Size of gene Ultramicroscopic particle? Some direct evidence Chromosomes not visible inside nucleus until division Work with x-rays Change in the gene as a result of being hit by photoelectron Effects  size of a single organic molecule

29. Gene definition Capacity of reproduction Little is known about gene reproduction Evidence from study of unstable genes: formation of new gene next to old one rather than division of old one Single molecule Transmission of hereditary characteristics Overall effect determined by all genes

30. Gene definition Location of genes Linear order Permanent locus Order changes =abnormalities Genetic distances ≠ actual distances Height Hair color Finger length Nail shape Eye color

31. Stability of the Gene Mutations Change from one allele to another Occur naturally, at very low rate X-rays and radiation increase that rate Different frequency in different genes “Unstable” genes Continuous series Rates differ in different tissues, and different stages of development.

32. Stability of the Gene

33. Experiment Two unstable genes for color, lavender and rose Both change to purple Number of purple spots  number of changes Size of the spots  stage of ontogeny when change occurred Lavender flowers, small spots  lavender gene unstable late in development Rose flowers, varying spots  unstable in all stages

34. Stability of the Gene Somatic vs. germ cell mutations Easier to observe large numbers of somatic cells Of two genes changing at the same rate, one which change in germ cells only will be “more stable” So “unstable” vs. “stable” higher frequency and change in tissues where easily detected

35. Role of genes Conclusion of studies: Any radical change eliminates the gene from the gene complex, and the elimination of a single gene usually is lethal Therefore… The primary function of gene is not the one by which we recognize it (determination of phenotypes), but the regulation of life processes of the cell!

36. 1970

37. Summary