Announcements

1. By 1924, approximately 3,000 people had been involuntarily sterilized in America; the vast majority (2,500) in California. “It is better for all the world, if instead of waiting to execute degenerate offspring for crime or to let them starve for their imbecility, society can prevent those who are manifestly unfit from continuing their kind…Three generations of imbeciles are enough.” Justice Oliver Wendell Holmes, Jr. U.S. Supreme Court; Buck vs. Bell, 1927 • Buck v. Bell supplied a precedent for the eventual sterilization of approximately 8,300 Virginians • sterilization of people in institutions for the mentally ill and mentally retarded continued through the mid-1970's. At one time or another, 33 states had statutes under which more than 60,000 Americans endured involuntary sterilization.

2. Announcements How is powerpoint slide printing going? Bring FlyLab to Lab next week; meet in Brooks 101 (computer lab) for the first part of lab Homework this week: Ch.2, problems 2, 10, 13, 14, 19 (NOT turned in) Answers to Ch.2 problems will be posted on Tuesday, Sept. 3 outside my office http://www.eugenicsarchive.org/html/eugenics/essay8text.html Quiz today!

3. Review of last lecture • Basic concepts that underlie the study of genetics: DNA, genes, chromosomes 2. Somatic cells have a diploid # of chromosomes (2n); • each chromosome type (except X and Y) exists as a homologous pair 3. Different forms of the same gene exist as alleles ex. wt vs. mutant CFTR gene 4. How do scientists investigate genetics? • 5. Genetics and society - eugenics, agriculture, medicine 6. Mitosis is one part of the cell cycle; important for many reasons 7. Four phases of mitosis: prophase, metaphase, anaphase, telophase

4. Outline of Lecture 3 I. Cell division is genetically regulated II. Meiosis III. Gregor Mendel - discovered basis for transmission of hereditary traits IV. Monohybrid cross V. Mendel’s postulates

5. I. Cell division is genetically regulated • Why are we interested in knowing how cell division is regulated? * if regulation is disrupted, uncontrolled cell division may result…..cancer • Most recent Nobel Prize was awarded to 3 scientists who studied genes that regulate the cell cycle, including Lee Hartwell (director of the Fred Hutchinson Cancer Research Center) who studied cell division regulation in yeast http://www.fhcrc.org/visitor/nobel/hartwell/accomplishments.html • There are 3 main checkpoints in the cell cycle

6. Three main checkpoints in the cell cycle Is cell the correct size? Is DNA damaged? 2. Is DNA fully replicated? Is DNA damage repaired? 3. Have spindle fibers formed? Have they attached to chromosomes correctly? 1. 3. 2.

7. Why are cell cycle checkpoints important? What might result if DNA repair has not finished? Uncontrolled cell division could occur - cancerous cell Example: p53 protein normally targets cells with severe DNA damage to undergo programmed cell death. (this removes them from the population) If the p53 gene is mutated, damaged cells will not be removed and may continue dividing in an uncontrolled manner. Many different types of cancers involve mutations of p53.

8. II. Meiosis a special cell division to make gametes (sperm and egg) Why would a “regular” mitosis be a problem in making gametes? If + then 4n 2n 2n sperm, egg embryo • Meiotic cell division generates cells (sperm and eggs) with one- half the genetic material (2n to 1n) - a reduction in chromosome number • Source of genetic variation - see mechanics

9. Key points of meiosis • Homologous chromosomes pair (synapse) to form a bivalent; the four chromosomes form a tetrad. • Recombination during meiosis is the basis for genetic variation within species. • Two divisions: reductional division and equational division, each with four phases

10. Mitosis vs. Meiosis • S phase: 2N  replication  duplicated 2N • Mitosis: duplicated 2N  separation of sister chromatids  each daughter cell is 2N • Meiosis: duplicated 2N  meiosis I (reduction division): separation of homologous chromosomes  synapsis of homologous chromosomes  recombination = duplicated N • meiosis II (equational division): duplicated N  separation of sister chromatids  N • Is Meiosis I or II more like mitosis?

11. Meiotic Prophase I(5 stages of prophase I) • 1. Leptonema “slender-thread” • Condensation: chromatin starts to condense • 2. Zygonema “paired-thread” • Pairing: homologues pair (synapsis) in synaptonemal complex (not in mitosis) • s.c. allows for crossing over; if it doesn’t form, no synapsis, no crossing over

12. Meiotic Prophase I (continued) 3. Pachynema “thick-thread” Ea. tetrad has 2 pr. sister chromatids Recombination: further condensation; crossing over occurs 4. Diplonema “doubled-thread” tetrads visible, chiasmata visible (where sister chromatids contact) 5. Diakinesis “movement apart” • Breakaway: sister chromatids pull apart, chiasmata move to ends of each tetrad • NEBD, nucleolus disappears, spindle fibers attach to centromeres

13. Completion of Meiosis I • Metaphase I • tetrads align randomly: independent assortment • Anaphase I • one-half of each tetrad, a dyad (homologue), moves to each pole • sister chromatids together • separation of tetrads is disjunction; when they do not separate it is nondisjunction - more ch. 10 • Telophase I Met I Ana I Tel I

14. Meiosis II • Mechanistically similar to mitosis. • Sister chromatids separate, producing monads. • Four haploid gametes can potentially form. • If crossing over occurred, ea. monad has combined genetic information

15. Gametogenesis:Spermatogenesis • Occurs after puberty, continuously in human males. • Equally-sized haploid products: sperm • Crossing over can occur to create genetic recombination.

16. Gametogenesis: Oogenesis • Begins during first months of embryogenesis in human females. • Meiosis arrests at diplotene of prophase I and resumes after puberty at ovulation. • Unequally-sized haploid products: huge egg and tiny polar bodies. • Meiosis arrests again at metaphase II and resumes after fertilization.

17. Multiple Choice - self test Which of the following is true about cell division: Meiosis I is more like mitosis because it is a reductional division (2n to 1n) Meiosis I is more like mitosis because sister chromatids separate Meiosis II is more like mitosis because it is an equational division (1n to 1n) Meiosis is similar to mitosis because it generates genetic variation

18. III. Gregor Mendel • Monastery of St. Thomas, Brno, Czech Republic. • Taught physics and natural science. • Performed experiments 1856-1868, published in 1866. • Why peas? • Easy to grow • Self-fertilize or can hybridize artificially • Matures in single season • Choice of contrasting traits

19. How Mendel performed his crosses with pea plants

20. Mendel’s 7 traits 1. 2. 3. 4. 5. 6. 7.

21. Modern genetic terminology • Phenotype - physical expression of a trait • Gene - Mendel’s “unit factors” of inheritance • Allele - different forms of a gene, e.g. D or d • Genotype - allelic composition of a trait • e.g. DD, Dd, or dd

22. More modern genetic terminology • Homozygous - genotype of identical alleles, e.g. DD or dd • Homozygote - homozygous individual • Heterozygous - genotype of different alleles, e.g. Dd • Heterozygote - heterozygous individual • Dominant and recessive - Alternative phenotypes when two alleles are expressed. • D is dominant and d is recessive if Dd and DD have the same phenotype

23. IV. Monohybrid cross (tall and dwarf pea plants)

24. Monohybrid Cross: Punnett Square Method • (1) Define symbols: • D = tall allele • d = dwarf allele • (2) State the cross • (3) Diagram the gametes • (4) Complete the squares • (5) Summarize the results: • Genotype • Phenotype

25. Reciprocal crosses • Results were the same regardless of which parent was used, e.g. • tall pollen pollinating dwarf eggs • dwarf pollen pollinating tall eggs • Therefore the results were not sex-dependent • Mendel proposed “unit factors” to explain his results

26. V. Mendel’s postulates Postulate 1. Unit factors in pairs • Genetic characters are controlled by unit factors in pairs. • In other words, genes are present in two associated copies in diploid organisms. • For example, DD plants have two alleles for tallness, dd plants have two alleles for dwarfism.

27. Postulate 2. Dominance/recessiveness • In the case of unlike unit factors, one can bedominant and the other can berecessive. • In other words, when two different alleles of a gene are present, one may show its effect while the other may be masked. • For example, Dd plants have a tall allele D and a dwarf allele d, but are phenotypically tall.

28. Postulate 3. Segregation • During the formation of gametes, unit factors segregate randomly. • In other words, when sperm and eggs are formed, one of each allelic pair is randomly distributed to to each gamete. • For example, a Dd plant makes pollen or eggs, each randomly receives either the D allele or the d allele.

29. Practice: Axial/Terminal Pods • In garden peas, an allele T for axial flowers is dominant to an allele t for terminal flowers. • In the F2 generation of a monohybrid cross, what is the expected ratio of axial : terminal? • Among the F2 progeny, what proportion are heterozygous? • Among the F2 progeny with axial flowers, what proportion are heterozygous?

30. Round/Wrinkled Seeds • Round (W) dominant to wrinkled (w) • What’s the molecular basis? Starch and sugar content • Wrinkled seeds have higher glucose, water content before drying, larger loss of seed volume during drying Loss-of-function in wrinkled allele