POST MENDELIAN GENETICS

ANNOUNCEMENTS

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

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

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

RedEyesIn FliesIs Normal(wild)

White Eyes Is Rare (mutation)

MORGAN & Drosophila• To Explore How Eye Color is Inherited in Flies Morgan

crossed:

All F1 Have Red Eyes

**Morgan concludes Red eye dominant to white eye allele.

Red-eyed Female

White-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 F2 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

XX

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 sperm

Gamete Formation In a Male Fly

MORGAN & DrosophilaThe 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 F1 genotype and phenotype of the following cross:

– Red-eyed Female x White-eyed Male

(homozygous)

SYMBOLS:Red eye = w+ Male =XYWhite eye = w Female =XX

IN CLASS EXERCISE

• Now, Perform Reciprocal Cross:

• White-eyed Female x Red-eyed Male

X

Mother Father Mother Father

Xw+Xw+ XwY

Male gametes Male gametes

XwXw Xw+Y

Xw Y Xw+ Y

Parental generationParental generation

Xw+

Xw+Xw Xw+Y Xw+Xw XwY Xw F1 generation

Fem

ale

gam

etes

Fem

ale

gam

etes

F1 generation

Resulting phenotypes: All offspring are red-eyed Resulting phenotypes: F1 females are red-eyed F1 males are white-eyed

Females Males MalesFemales

First half of reciprocal cross Second half of reciprocal cross

MORGAN & Drosophila

Red eye allele = w+White eye allele = w

Female = XXMale = XY

IN CLASS EXERCISE

• Finally, cross F1 progeny from original cross:

• Red-eyed Female x Red-eyed Male

X

Crossing the F1 offspring :

F1 generation

Mother Father

Xw+ YMale gametes

Fem

ale

gam

etes

Xw+Xw+ Xw+Y

XwY Xw+Xw

Xw+

Xw

F2 generation

Females Males

Resulting phenotypes: All F2 females are red-eyed 1/2 of F2 males are red-eyed

Xw+Xw Xw+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+ w+

y y

w w

y+ y+ y y

w+ w+

y yy+y+

w w

Hypothesis (Morgan): When two genes occur on onechromosome (linked), INDEPENDENTASSORTMENT DOES NOT OCCUR

AFemale(2X chromo)

White eyes

Gray body

Red eyes

Yellow body

Gam

etes

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 w

y+ y+

w+ w+

Results of cross are notAs Morgan predicted!!

Parentalgeneration

F1 generation

F2 generation MALES

Meiosis I

Meiosis II

w w w+ w+

y+y+ yy

Phenotype Genotype Number

Female Male

Female MaleX

X

Hypothesis: When two loci occur on one chromosome,meiosis results in two, rather than four, types ofgametes because independent assortment does not occur.

Novelgenotypes

w+w+

w+w+ww

w w

y y

yyy+y+

y+ y+

Xwy+ /YXw+y /YXwy /YXw+y+/Y

4292

4605

44

8686

Xwy+/ Xw+y Xwy+/ Y

Xw+y / YXwy+/ Xwy +

w+ywy+

Gam

etes

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

RECOMBINATIONGenetic Recombination:• Production of offspring with a

new combination of traits

– Linked genes become unlinked through recombination

• Ex: Crossover (during meiosis)

w w+

Y+ y Y+ y

w+ w+ww

Y+ y yY+

Crossing overduring meiosis I

Meiosis II

w+ w+w w

Y+ Y+ y y

wy+ wy w+ y+ w+yRecombinant chromosomes

Gam

etes

Recombination provides explanation for unexpected phenotypes in F2 males

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

Morgan’sAssumption: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 1 Gamete 2

w

y+

w+

y+

RECOMBINATION

• A cross over event results in 2 new combinations:

w+

y+

w

yy+

w+Meiosis I & II +

w

y

Parent Cell

Recombinant Gametescrossover

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 B C 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 1Gene 2Gene 3Gene 4Gene 5Gene 6Gene 7Gene 8Gene 9Gene 10Gene 11Gene 12

Crossing over rarelyoccurs betweenadjacent loci, recombinationsare rare.

Crossing overalmost alwaysoccurs betweendistant loci, recombinationsare frequent.

0 : Yellow body0 : Yellow body1.4 : White eyes

Map units

0 : Yellow body1.4 : White eyes

20 : Cut wings

Chromosomes arecomposed of genes The physical distance

between loci determinesthe frequency of crossingover.

Frequency of crossingcan be used to mapphysical between loci.

Linkage map

GENE MAPPING % recombinant gametes reflectsdistance 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