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POST MENDELIAN GENETICS

POST MENDELIAN GENETICS. ANNOUNCEMENTS. Genetics Problems (set #2) will be posted Fri. . OBJECTIVES. Be familiar with contribution of early 20 th century biologists to field of genetics Be able to predict patterns of inheritance for genes located on sex chromosomes

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POST MENDELIAN GENETICS

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  1. POST MENDELIAN GENETICS

  2. ANNOUNCEMENTS • Genetics Problems (set #2) will be posted Fri.

  3. OBJECTIVES • Be familiar with contribution of early 20th century biologists to field of genetics • Be able to predict patterns of inheritance for genes located on sex chromosomes • Understand the concept of “Linked Genes” • Understand how recombination of genes affect genetic variability • Understand how frequency of recombination of linked genes is related to their distance from one another

  4. THE CHROMOSOME THEORY OF INHERITANCE • Walter Sutton & Theodor Boveri (1903): • Movement of chromosomes during meiosis provides the physical basis for Mendel’s principles

  5. EXTENDING THE CHROMOSOME THEORY • Thomas Hunt Morgan: • Drosophila melanogasteras a model species: • Small size • Easy to culture • Short reproductive cycle (10 days) • Abundant progeny • Developed external anatomy

  6. MORGAN & Drosophila Morgan Revealed Extensions of Mendel’s Rules: • Eye color linked to sex of progeny!

  7. MORGAN’S WORK WITH Drosophila Red Eyes In Flies Is Normal (wild) White Eyes Is Rare (mutation) Morgan discovered a white eyed male (mutant phenotype)

  8. MORGAN & Drosophila • To Explore How Eye Color is Inherited in Flies Morgan crossed: • Red-eyed Female X White-eyed Male **Morgan concludesRed eyedominantto white eye allele. All F1 Have Red Eyes

  9. MORGAN & Drosophila • Next, Morgan crossed F1: Red-eyed Female Red-eyed Male X Only MALE Progeny Had WHITE EYES!!!

  10. MORGAN & Drosophila • To test if sex and eye color were linked, Morgan crossed : Red-eyed Females (from F1) X White-eyed Males Morgan concludes BOTH sexes canhave WHITE eyes Some F2 FEMALES had White eyes

  11. MORGAN & Drosophila • However, Reciprocal Cross Produced Different Results! White-eyed Females X Red-eyed Males (from F1) Allmales had WHITE eyes (all females had red) Morgan concludes EYE Color & SEX are LINKED!!!

  12. THE DISCOVERY OF SEX CHROMOSOMES Nettie Stevens: Observed differences in chromosomes between male & female beetles (Tenebrio molitor) • Chromosomes named X and Y: • Half male gametes contain Y, other half X • Male = the heterogametic sex • All female gametes contain X • Female = the homogametic sex

  13. THE DISCOVERY OF SEX CHROMOSOMES Nettie Stevens: • Developed hypothesis about sex determination: • Male is formed when egg is fertilized by sperm carrying Y • Female is formed when egg fuses with X carrying sperm X X Y

  14. NORMAL SEX CHROMOSOMES A Male

  15. BACK TO MORGAN… Gamete Formation In a Male Fly Morgan guessed that D. melanogaster (like T. molitor) had chromosomes that differ between sexes: • Male flies carry X and Y chromosome (XY) • Females carry 2 X (XX) sperm sperm

  16. MORGAN & Drosophila The X Linked Hypothesis: • Morgan hypothesized that gene controlling eye color is located onX chromosome: • Females have 2 copies of gene for eye color: • Only homozygous recessive females exhibit white eyes • Males have 1 copy (contributed by mom): • Males with ONE ALLELE for white eyes exhibit white eyes!

  17. IN CLASS EXERCISE • Apply techniques learned in class (i.e. Punnet Square) to predict F1 genotype and phenotype of the following cross: • Red-eyed Female x White-eyed Male (homozygous) SYMBOLS: Red eye = w+ Male =XY White eye = w Female =XX

  18. IN CLASS EXERCISE • Now, Perform Reciprocal Cross: • White-eyed Female x Red-eyed Male X

  19. MORGAN & Drosophila First half of reciprocal cross Second half of reciprocal cross Father Mother Mother Father Parental generation Parental generation Xw+Xw+ XwY XwXw Xw+Y Male gametes Male gametes Y Xw Y Xw+ Xw+ Xw F1 generation F1 generation Female gametes Female gametes Xw+Xw XwY Xw+Xw Xw+Y Females Males Females Males Resulting phenotypes: F1 females are red-eyed F1 males are white-eyed Resulting phenotypes: All offspring are red-eyed Female = XX Male = XY Red eye allele = w+ White eye allele = w

  20. IN CLASS EXERCISE • Finally, cross F1 progeny from original cross: • Red-eyed Female x Red-eyed Male X

  21. MORGAN & Drosophila Crossing the F1 offspring : Mother Father F1 generation Xw+Xw Xw+Y Male gametes Y Xw+ Xw+ Xw+Xw+ Xw+Y F2 generation Female gametes Xw Xw+Xw XwY Females Males Resulting phenotypes: All F2 females are red-eyed 1/2 of F2 males are red-eyed

  22. MORGAN & Drosophila Morgan’s work with Drosophila provided evidence that: • The X chromosome contains genes the Y doesn’t: • Inheritance patterns of sex-linked genes vary between sexes • Recessive traits more prevalent in males • Genes are located on chromosomes • Later supported by other scientists

  23. LINKAGE • Linkage: • Physical association of genes found on theSAME chromosome that influence different traits

  24. LINKED GENES • Linked genes are those that reside on the same chromosome and tend to be inherited together: • Autosomal Genes: • Reside on the autosomal chromosomes • In humans: genes are located on chromosome #1-22 • Sex-Linked Genes: • Found on sex chromosomes • In humans: genes found on pair #23 (usually on the X)

  25. MORGAN & LINKED GENES • First examples of linked genes were found on X chromosome of Drosophila: • Morgan established that eye color & body color are linked traits • Both found on X chromosome of fruit fly

  26. MORGAN & LINKED GENES • Morgan re-evaluated Mendel’s Principle of Independent Assortment • Morgan predicted: • Linked genes should be transmitted together during gamete formation • Genes on the same chromosome should NOT undergo independent assortment

  27. LINKAGE HYPOTHESIS White eyes A Female (2X chromo) w+ w+ Red eyes Body Color: Gray body = wild type (y+) Yellow body = mutant (y) w w Hypothesis (Morgan): When two genes occur on one chromosome (linked), INDEPENDENT ASSORTMENT DOES NOT OCCUR Gray body y y y+ y+ Yellow body Eye Color: Red = wild type (w+) White = mutant (w) Meiosis I w+ w+ w w y+ y+ y y Meiosis II w+ w+ w w Gametes y y+ y+ y wy+ w+y ONLY 2 gamete types

  28. MORGAN’S TEST OF THE LINKAGE HYPOTHESIS Linkage hypothesis Results of cross are notAs Morgan predicted!! Result of Cross: NOT As Morgan Predicted! Female Male X Parental generation White eyes Red eyes w+ w+ w w Xwy+/ Xwy+ Xw+y / Y Gray body Yellow body y+ y+ y y Female Male F1 generation X Meiosis I w+ w w w+ Xwy+/ Y Xwy+/ Xw+y y+ y+ y y • Eye Color: • Red = wild type (w+) • White = mutant (w) F2 generation MALES  Phenotype Genotype Number Meiosis II Xwy+ /Y 4292 Xw+y /Y w w w+ w+ 4605 Gametes y y y+ y+ Xwy /Y Novel genotypes 86 86 Xw+y+/Y 44 w+y wy+ Hypothesis: When two loci occur on one chromosome, meiosis results in two, rather than four, types of gametes because independent assortment does not occur. Results: There are four kinds of male offspring rather than two!! • Body Color: • Gray body = wild type (y+) • Yellow body = mutant (y)

  29. LINKAGE HYPOTHESIS • Results of test could NOT be explained by the linkage hypothesis alone. • Two of four (male) phenotypes NOT predicted • Crossovers during Meiosis I may be the answer

  30. RECOMBINATION Genetic Recombination: • Production of offspring with a new combination of traits • Linked genes become unlinked through recombination • Ex: Crossover (during meiosis)

  31. Morgan’s Assumption: w linked to y+ w+ linked to y There are four kinds of gametes (eggs) rather than two due to crossing over in small % of F1 females (during Meiosis I) Female Cell  2 X Chromosomes w w+ y Y+ Y+ y Crossing over during meiosis I w w w+ w+ Y+ y Y+ y Meiosis II w w w+ w+ Gametes y Y+ Y+ y wy w+ y+ wy+ w+y Recombinant chromosomes Recombinationprovides explanation for unexpected phenotypes in F2 males

  32. RECOMBINATION • In absence of crossing over, there are 2 types of gametes (as predicted by Morgan): w w+ w Meiosis I & II w+ + y+ y y+ y Gamete 1 Gamete 2 Parent Cell

  33. RECOMBINATION • A cross over event results in 2 new combinations: w w+ Meiosis I & II w+ w + y+ y y+ y crossover Recombinant Gametes Parent Cell

  34. RECOMBINATION PROBABILITY • The farther apart two genes, the higher the probability they will be separated during crossover: • Genes far apart on chromosome are more likely to beseparated • Genes close together are less likely to be separated

  35. RECOMBINATION PROBABILITY • A & D are more likely than B & C to become separated (unlinked) • B & C more likely to be inherited together (stay linked) B C A D

  36. GENE MAPPING • Maps of genes can be constructed from recombination data • Recombination data reflects “distance” between 2 loci Linkage map: genetic map based on recombination frequencies Crossing Over

  37. GENE MAPPING % recombinant gametes reflects distance between 2 loci Gene 1 Crossing over rarely occurs between adjacent loci, recombinations are rare. 0 : Yellow body 0 : Yellow body 0 : Yellow body Gene 2 1.4 : White eyes 1.4 : White eyes Gene 3 Gene 4 Map units Gene 5 Gene 6 Gene 7 20 : Cut wings Crossing over almost always occurs between distant loci, recombinations are frequent. Gene 8 Gene 9 Gene 10 Gene 11 Gene 12 Linkage map Chromosomes are composed of genes The physical distance between loci determines the frequency of crossing over. Frequency of crossing can be used to map physical between loci.

  38. GENE MAPPING • If % ofrecombinant gametes is high, 2 genes are assumed to be far apart on a chromosome • Map Unit refers to distance between 2 loci • Function of % recombinants

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