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
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
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