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 self-fertilization– can produce pure lines

• Offspring always have one of the parental traits

X

100%

F1

P

XF1

75%

F2 +

25%

XF1

75%

F2 +

25%

Xaa AA

Aa Aa

aa25% AA50%Aa

P

Xaabb AABBP

XF1 AaBb AaBb

F2aaBbaaBBaabb

AABBAABbAaBbAaBB

AAbbAabb

6%1

19%3

56%9

19%3

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 AB ab Ab

1 : 1 1 : 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

2 possible combinations of chromosomes to form gametes > 8,000,000 different gametes

23

When two gametes combine (fertilization), there are approximately (8 million) combinations2

Actual # of possible combinations of zygotes (fertilized eggs) in humans = 70, 368, 744, 177, 664

Somatic vs Germ Cells

2n 2n

2n

4n

Somatic (body) vs Germ Somatic (body) vs Germ (reproductive) Cells(reproductive) Cells

2n

4n

2n 2n2n 2n

2n

4n

2n 2nn n2n 2nn n

Mitosis

(no change)

Mei

osis

(cha

nge)

No

shuf

flin

g

Shuffling

Somatic vs Germ Cells

46 46

46

92

Somatic (body) vs Germ Somatic (body) vs Germ (reproductive) Cells in Humans(reproductive) Cells in Humans

2n

4n

2n 2n46 46

46

92

2n 2n23 232n 2n23 23

Mitosis

(no change)

Mei

osis

(cha

nge)

No

shuf

flin

g Shuffling

Crossing Over in MeiosisAnother Way to Generate Variation

Genes on the same chromosomeare linked - independence of segregationdepends on distance and frequency of crossing-over

From DNA to Protein

DNA Base PairsA-C-G-T

Triplet Codonsfor (20) Amino Acids

AAA - CAT etc.

RNAIntermediaries

Protein(polymer of Amino Acids)

What Proteins Do….• Provide structure

• Catalyze reactions

• Recognize molecules

• Transport molecules

• Regulate gene expression

• 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

MutationPoint Mutations

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, Sickle-Cell)

• Frequency: about one in a million amino acids

Three Genetic Mutations

Substitution

Insertion

Deletion AATAAGAA AATAGAA

AATAAGAA AATATGAA

AATAAGAA 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 self-fertilizing or inbreeding species, especially plants

• 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 ?? )

Human genomes are complex, but ….

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

Trait value

Fre

quen

cy

Mean

Trait value

Fre

quen

cy

Old Mean

Parents Offspring

Directional Selection may reduce variation, shifts mean

Trait value

Fre

quen

cy

Mean

Trait value

Fre

quen

cy

Old Mean

Parents Offspring

Disruptive Selectionincreases variation, may shift mean

Trait value

Fre

quen

cy

Mean

Parents Offspring

Trait value

Fre

quen

cy

Old Mean

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