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 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

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

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

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

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

MORGAN & Drosophila To Explore How Eye Color is Inherited in Flies Morgan crossed: All F 1 Have Red Eyes **Morgan concludes Red eye dominant to white eye allele. Red-eyed FemaleWhite-eyed Male X

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

MORGAN & Drosophila To test if sex and eye color were linked, Morgan crossed : Red-eyed Females (from F1) X White-eyed Males Some F 2 FEMALES had White eyes Morgan concludes BOTH sexes can have WHITE eyes

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

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

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

NORMAL SEX CHROMOSOMES A Male

BACK TO MORGAN… 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 Gamete Formation In a Male Fly

MORGAN & Drosophila The X Linked Hypothesis: Morgan hypothesized that gene controlling eye color is located on X 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!

IN CLASS EXERCISE Apply techniques learned in class (i.e. Punnet Square) to predict F 1 genotype and phenotype of the following cross: –Red-eyed Female x White-eyed Male (homozygous) SYMBOLS: Red eye = w+Male =XY White eye = wFemale =XX

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

Mother Father Mother Father Xw+Xw+Xw+Xw+ XwYXwY Male gametes XwXwXwXw X w+ Y XwXw YX w+ Y Parental generation Xw+Xw+ Xw+XwXw+Xw Xw+YXw+Y Xw+XwXw+Xw XwYXwY XwXw F 1 generation Female gametes F 1 generation Resulting phenotypes: All offspring are red-eyed Resulting phenotypes: F 1 females are red-eyed F 1 males are white-eyed FemalesMales Females First half of reciprocal cross Second half of reciprocal cross MORGAN & Drosophila Red eye allele = w+ White eye allele = w Female = XX Male = XY

IN CLASS EXERCISE Finally, cross F 1 progeny from original cross: Red-eyed Female x Red-eyed Male X

Crossing the F 1 offspring : F 1 generation MotherFather X w+ Y Male gametes Female gametes X w + X w+ Xw+YXw+Y XwYXwYXw+XwXw+Xw X w+ XwXw F 2 generation FemalesMales Resulting phenotypes: All F 2 females are red-eyed 1/2 of F 2 males are red-eyed Xw+XwXw+Xw Xw+YXw+Y 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 MORGAN & Drosophila

LINKAGE Linkage: –Physical association of genes found on the SAME chromosome that influence different traits

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)

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

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

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

Results of cross are not As Morgan predicted!! Parental generation F 1 generation F 2 generation MALES  Meiosis I Meiosis II w w w+w+ w+w+ y+y+ y+y+ yy PhenotypeGenotypeNumber FemaleMale FemaleMale X X Hypothesis: When two loci occur on one chromosome, meiosis results in two, rather than four, types of gametes because independent assortment does not occur. Novel genotypes w+w+ w+w+ w+w+ w+w+ w w ww y y yy y+y+ y+y+ y+y+ y+y+ X wy + /Y X w + y /Y X wy /Y X w+y+ /Y X wy + / X w+y X wy+ / Y X w+y / Y X wy + / X wy + w+yw+y wy + Gametes Red eyes Yellow bodyGray body White eyes Linkage hypothesis MORGAN’S TEST OF THE LINKAGE HYPOTHESIS Eye Color: Red = wild type (w+) White = mutant (w) Result of Cross: NOT As Morgan Predicted! Body Color: Gray body = wild type (y+) Yellow body = mutant (y) Results: There are four kinds of male offspring rather than two!!

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

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

ww+ Y+ y y w+ ww Y+y y Crossing over during meiosis I Meiosis II w+ ww Y+ y y wy+ wyw+ y+ w+y Recombinant chromosomes Gametes Recombination provides explanation for unexpected phenotypes in F 2 males There are four kinds of gametes (eggs) rather than two due to crossing over in small % of F 1 females (during Meiosis I) Female Cell  2 X Chromosomes Morgan’s Assumption: w linked to y+ w+ linked to y

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

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

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 be separated –Genes close together are less likely to be separated

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

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

Gene 1 Gene 2 Gene 3 Gene 4 Gene 5 Gene 6 Gene 7 Gene 8 Gene 9 Gene 10 Gene 11 Gene 12 Crossing over rarely occurs between adjacent loci, recombinations are rare. Crossing over almost always occurs between distant loci, recombinations are frequent. 0 : Yellow body 1.4 : White eyes Map units 0 : Yellow body 1.4 : White eyes 20 : Cut wings 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. Linkage map GENE MAPPING % recombinant gametes reflects distance between 2 loci

GENE MAPPING If % of recombinant 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