Download Gregor Mendel (1822-1844) & the Foundations of Genetics

Gregor Mendel (1822-1844)
& the Foundations of Genetics
Early Views of Inheritance
• The Humunculus - in the egg or sperm?
• Pangenesis - the mechanism of acquired inheritance –
each tissue has its own genes, which migrate to the egg &
sperm
• Blended Inheritance - characters take on characteristics
of both parents
Why Mendel Liked Peas
• Several variable characters with two
discrete traits
– easy to score (yellow or green)
• Can control fertilization, including selffertilization
– can produce pure lines
• Offspring always have one of the parental
traits
P
X
F1
100%
F1
X
F2
+
25%
75%
P
F1
F2
aa
X
Aa
X
aa
25%
+
AA
Aa
25% AA
50%Aa
75%
F2
P
aabb
X
F1
AaBb
X
AABB
AaBb
aabb
aaBb
aaBB
AAbb
Aabb
6%
1
19%
3
19%
3
AABB
AABb
AaBb
AaBB
56%
9
Mendel’s Inferences
• Alternate traits caused by alternate forms of genes, the unit
of heredity
• An organism has two genes, one from each parent, for
each character
– can produce pure lines
• Offspring always have one of the parental traits
• Sperm & eggs always have just one allele (gene variant),
because they segregate
• When two alleles are different, one is fully expressed and
one is masked (dominant or recessive)
Mendel’s First Conclusion:
Law of Segregation
• All allele pairs randomly segregate during
gamete formation
• Paired condition restored with fusion
(fertilization)
Aa
A
a
1
:
1
Mendel’s Second Conclusion:
Law of Independent Assortment
• Each allele pair segregates independently of
all others
AaBb
aB
1
AB
:
1
ab
:
1
Ab
:
1
Chromosomes are the location
of genes
• Chromosomes: long, threadlike associations
of genes found in the nucleus consisting of
protein & DNA
• Mendel’s Laws hold for chromosomes, within
chromosomes there is some shuffling, called
crossing-over
• Humans: 46 chromosomes - 22 pairs of
autosomes plus 2 sex chromosomes (X and Y)
Mendel’s Laws are a powerful
source of variation
23
2 possible combinations of chromosomes to form
gametes > 8,000,000 different gametes
When two gametes combine (fertilization), there are
approximately (8 million) 2 combinations
Actual # of possible combinations of zygotes
(fertilized eggs) in humans = 70, 368, 744, 177, 664
No shuffling
(change)
2n
4n
2n
2n
2n
n
2n
n
Shuffling
2n
Mitosis
4n
(no change)
2n
Meiosis
Somatic (body) vs Germ
Somatic vs Germ Cells
(reproductive) Cells
2n
2n
n
2n
n
No shuffling
(change)
2n
46
4n
92
2n
46
2n
46
2n
23
2n
23
Shuffling
46
Mitosis
92
(no change)
46
Meiosis
Somatic (body) vs Germ
Somatic vs Germ Cells
(reproductive) Cells in Humans
46
2n
23
2n
23
Crossing Over in Meiosis
Another Way to Generate Variation
Genes on the same chromosome
are linked - independence of
segregation
depends on distance and frequency of
crossing-over
From DNA to Protein
DNA Base Pairs
A-C-G-T
Protein
(polymer of Amino Acids)
Triplet Codons
for (20) Amino Acids
AAA - CAT etc.
RNA
Intermediaries
What Proteins Do….
•
•
•
•
•
Provide structure
Catalyze reactions
Recognize molecules
Transport molecules
Regulate gene
expression
Mutation
Point Mutations
• Change in one base pair - may or may not
change amino acid, changed amino acid
may or may not change protein
conformation
• Spontaneous, but also increased by
radiation, heat, chemical mutagens
• Rate ‘Infrequent’: one in a billion bases
AATAAGAA
AATATGAA
Detectable Genetic Mutations
• Many amino acid substitutions do not effect a
protein’s function - they are silent
• Non-silent substitutions affect the proteins
conformation (shape) or expression (promote or
stop)
• Sometimes silent substitutions become revealed
when the environment is changed
• Many important genetic diseases (e.g. PKU, SickleCell)
• Frequency: about one in a million amino acids
Three Genetic Mutations
Deletion
AATAAGAA
Substitution AATAAGAA
Insertion
AATAAGAA
AATAGAA
AATATGAA
AATAAAGAA
Chromosomal Mutations
• Chromosomes can be duplicated, portions can be
translocated to a different chromosome or inverted
on the same, or deleted
• Usually has profound consequences - sterility or
worse
• Common, e.g. Down’s syndrome 1:700 births
• Major mode of ‘instantaneous’ speciation in selffertilizing or inbreeding species, especially plants
Human genomes are complex, but ….
• Only 1/3 more genes than a worm
- Genes like components in assembly lines?
• Many more harmful mutations per generation
• Much less coding DNA (rest junk or spacer or ?? )
Genetic Load
• For humans, estimated by reduced fertility and increase in
birth defects associated with conceptions between relatives
• 4 recessive lethals per individual, more than one new lethal
per generation
• In women’s eggs, chromosomal defects in eggs increase
with age
• In men’s sperm, DNA sequence changes increase with age
• In outbred human conceptions
– 70% of conceptions never come to term
– 2 per 1000 live births have genetic defects
What Changes Gene Frequencies?
•
•
•
•
•
Mutation
Genetic drift (random change in small pops)
Non-random Mating
Migration = Gene Flow
Natural Selection
Purifying Selection
• Dominant or Sex-linked (X or Y) deleterious mutant
alleles eliminated rapidly by natural selection
• Recessive autosomal deleterious mutant alleles
reduced slowly by selection
– heterozygotes ‘protect’ recessive deleterious mutant
alleles
– never eliminated: a mutation - selection equilibrium is
reached
Stabilizing Selection
decreases variation, doesn’t shift mean
Old Mean
Frequency
Frequency
Mean
Trait value
Trait value
Parents
Offspring
Directional Selection
may reduce variation, shifts mean
Old Mean
Frequency
Frequency
Mean
Trait value
Trait value
Parents
Offspring
Disruptive Selection
increases variation, may shift mean
Old Mean
Frequency
Frequency
Mean
Trait value
Trait value
Parents
Offspring
Sexual Selection
Forms of Sexual Selection
• Intrasexual (usually male-male
competition)
– Weapons for within-sex competition
• Intersexual (usually females
choosing males)
– Ornaments or signals to attract
choosy mates
– Why are animals choosy: aesthetic
preferences (Darwin’s hyp.) or
signals indicate mate quality?
Consequences of Sexual Selection
• Drives species away from the ecological
optimum
• Major cause of sexual dimorphism via
disruptive selection: since ornaments are
an advantage in only one sex, there is
selection for modifiers that lead to
expression in one sex only