Você está na página 1de 53




Radhika Reddy, PhD


1. Population genetics: Allele frequencies in populations
a. The Hardy Weinberg Principle
b. Exceptions to the HWP: X linked genes, inbreeding
c. A practical application of allelic frequency calculation:
DNA typing
2. Evolution: changes in allele frequency over time
a. Natural Selection
b. Fitness
c. Genetic drift
d. Molecular evolution

Crash Course “When Darwin met Mendel”: https://www.khanacademy.org/partner-content/crash-

course1/crash-course-biology/v/crash-course-biology-117 0:00 to 5:00
Population Genetics
Population genetics = application of
genetic principles to entire
populations of organisms

Population = group of organisms of

the same species living in the same
geographical area

Subpopulation = any of the breeding

groups within a population among
which migration is restricted

Local population = subpopulation

within which most individuals find
their mates
How Are Populations, Genes, and Evolution
• Evolution is not a property of individuals, but of populations
(members of a species in a given area)
• Inheritance of genes provides the link between the lives of
individual organisms and the evolution of populations

Genes (genotype)
and the environment
interact to determine
traits (phenotype)
Coat color in hamsters illustrates the interaction
between genotype and phenotype
• Dominant allele: enzyme for black pigment
• Recessive allele: enzyme for brown pigment
The gene pool comprises all of the alleles in a
population: the hamster example continued
25 hamsters
50 alleles
• 20 of those 50
alleles code for
black coats
• frequency of the
black allele = 20/50
= 0.40 = 40%
NOTE: don’t confuse mendelian
genetics (where punnett squares
are predictive for individuals) with
population genetics, where
predictions rely on observed gene
Evolution is the change of allele frequencies
within a population over time

Evolving Population: allele frequencies change from one

generation to the next
Equilibrium population: allele frequencies do not change
from generation to generation and the following conditions
are met:
1. No mutations
2. No gene flow (immigration/emmigration)
3. The population must be very large
4. Mating must be random, with no tendency for certain
genotypes to mate with specific other genotypes
5. No natural selection

Bozeman Science on Hardy Weinberg (long) http://www.bozemanscience.com/hardy-weinberg-equation/

Population Genetics
Gene pool: the complete set
of genetic information in all
individuals within a population
Genotype frequency:
proportion of individuals in a
population with a specific
Genotype frequencies may
differ from one population to
Allele frequency: proportion
of any specific allele in a
Population Genetics
The allele frequencies among gametes equal those
among reproducing adults.

Calculation of the allele frequencies in gametes.

Hardy–Weinberg Proportion
When gametes containing either of two alleles, A or a, unite
at random to form the next generation, the genotype
frequencies among the zygotes are given by the ratio
p2 : 2pq : q2

This are the Hardy–Weinberg (HW) Proportions

p = frequency of a dominant allele A

q = frequency of a recessive allele a
p + q =1

Crash Course “when Darwin met Mendel”: https://www.khanacademy.org/partner-content/crash-

course1/crash-course-biology/v/crash-course-biology-117 5:00 to end
Hardy Weinberg Web Activity: http://highered.mcgraw-
A solved problem
The Hardy–Weinberg law:
1. frequency of the alleles
in the gene pool does not
change over time
2. After one generation of
random mating,
frequencies for two
alleles can be calculated
as p2  2pq  q2  1

• p equals the frequency of

allele A.
• q is the frequency of allele
A solved problem
A single autosomal allele with two alleles A, a
• Frequency of A  0.7 and a  0.3. Note: A  a  1
• AA  (0.7)  (0.7)  0.49
• Aa  (0.7)  (0.3) (2)  0.42
• aa  (0.3)  (0.3) = 0.09 or 9 percent will be recessive
Solved problem #2: the ccr5 gene mutation
The CCR5 gene encodes a receptor for strains of HIV-1,
allowing it to gain entry into cells
The ∆32 mutation in CCR5 renders a person less
susceptible to HIV-1
Solved problem #2: the ccr5 gene mutation

Genotypes were determined by direct DNA analysis using

PCR and restriction-enzyme digest analysis
Solved problem #2: the ccr5 gene mutation

P= 0.89, q=.11 HW prediction: p2  2pq  q2  1

(.89x.89) + 2(.89)(.11) + (.11)(.11) = .79 + .20 + .01 = 1
Hardy–Weinberg Principle:
Multiple alleles

Frequency of any
genotype equals
square of allele
frequency = pi2

Frequency of any
genotype equals 2 
product of allele
frequencies = 2pipj
Solved problem #3: the ABO blood group

For three alleles (p  q  r  1), the frequencies of the

genotypes are given by
(p  q  r)2  p2  q2  r2  2pq  2pr  2qr
If a population in Hardy–Weinberg equilibrium
has an aa genotype frequency of 0.64, what is the
frequency of the a allele?

A. 0.2
B. 0.33
C. 0.5
D. 0.67
E. 0.8

© 2013 Pearson Education, Inc.

If a population in Hardy–Weinberg equilibrium
has an aa genotype frequency of 0.49, what is the
frequency of the Aa genotype?

A. 0.2
B. 0.42
C. 0.5
D. 0.7
E. 0.8

© 2013 Pearson Education, Inc.

Now Solve This
TIP: When you know the frequency of the recessive
phenotype = q2. This enables you to calculate q, and
subsequently p.
tt: 37/125=.296
√.296 = .544 = q2
Hardy–Weinberg Principle
One important implication of the HW Principle is that allelic
frequencies will remain constant over time if the following
conditions are met:
1. The population is sufficiently large
2. Mating is random
3. Allelic frequencies are the same in males and females
4. Selection does not occur, i.e., all genotypes have equal
in viability and fertility
5. Mutation and migration are absent
Hardy–Weinberg Principle
Another important
implication is that for a
rare allele, there are
many more
heterozygotes than there
are homozygotes for the
rare allele

Consider 2pq vs q2 as q
becomes smaller and p
becomes larger

Allele frequency graphs.

Hardy–Weinberg Principle:
X-linked genes
males have only one X-

Male genotype frequencies =

allele frequencies:
H = p, h = q

Female genotype frequencies

HH = p2 ; Hh = 2pq; hh = q2
Hardy–Weinberg Principle:
X-linked genes
An important implication: if h is a rare recessive allele,
then there will be many more males exhibiting the trait (q)
than females (q2)
*** Take this with a grain
of salt. X inactivation
results in partial affected
vs. non affected

The ratio of affected males

to affected females
increases as the allele
frequency decreases.
Inbreeding (mating between relatives) results in an excess of
homozygotes compared with random mating

In most species, inbreeding

is harmful due to rare
recessive alleles that
wouldn’t otherwise become

An inbreeding pedigree.
Effect of inbreeding on genotype frequencies. The large rectangles on the left
pertain to alleles whose ancestries are not affected by inbreeding.
Inbreeding: Inbreeding Coefficient
Inbreeding coefficient F = (2pq – HI )/2pq, where HI = frequency
of heterozygous genotypes in an inbred population.

F=1→complete inbreeding
Genotype F=0→no inbreeding.
frequencies in
inbred population:
AA: p2(1 – F) + pF
Aa: 2pq(1 – F)
aa: q2(1 – F) + qF
Sewall Wright devised the coefficient of
• F: probability that the two alleles of a given gene in an
individual are identical because they are descended from the
same single copy of the allele in an ancestor.
• If F = 1, all individuals in the population are homozygous, and
both alleles in every individual are derived from the same
ancestral copy.
• If F = 0, no individual has two alleles derived from a common
ancestral copy.

Inbreeding results in decreased heterozygosity

Case example: F=1

Self fertilizing plant
Effects of repeated
self-fertilization on the
genotype frequencies.
In each generation,
the proportion of
decreases to half.

AA: p2(1 – F) + pF = p2(1 – 1) + p(1) = 0 + p = p = 1/2

Aa: 2pq(1 – F) = 2pq(1 – F) = 0
aa: q2(1 – F) + qF= q2(1 – 1) + q(1) = 0 + q = 1/2
Graph on the effect of first-cousin mating on the frequency of
offspring genotype.
Allelic Variation
Allelic variation length of simple tandem repeat (STR)
STRs generate fragments of different sizes which can be used
to map DNA since they
DNA Typing
The use of polymorphisms in DNA
to link suspects with samples of
human material is called DNA
1. Highly polymorphic
sequences are used in DNA
2. Polymorphic alleles may
differ in frequency among
subpopulations due to
population substructure
3. DNA exclusions are
NYTimes on DNA Typing: http://www.nytimes.com/2014/05/19/us/dna-analysis-exposes-an-
Evolution : changes in the allele frequencies present in a
Four processes account for most evolutionary changes
1. Mutation = the ultimate source of genetic variation
2. Migration = the movement of organisms among
3. Natural selection = genotypes best suited to survive and
reproduce in a particular environment give rise to a
disproportionate share of the offspring
4. Random genetic drift = the random, undirected changes
in allele frequencies, especially in small populations
Natural Selection
Natural selection rests on three premises:
1. More organisms are produced than can survive and
2. Organisms differ in their fitness, the ability to survive and
reproduce, and some of these differences are due to
3. The genotypes that promote survival are favored and
contribute disproportionately to the offspring of the next
Relative fitness: contribution of
each parental genotype to the pool
of offspring genotypes in each
Selection coefficient: degree of
disadvantage of a disfavored
Natural Selection
• Natural selection (Charles Darwin,1858):
Hereditary differences among organisms
influences their ability to survive and reproduce
in the prevailing environment.
• Adaptation = progressive genetic
improvement in populations due to natural

• The selection coefficient: the difference

between the fitness of the standard (=1) and
that of the genotype (>1 if selection is
occurring) in question

Increase in frequency of a favored strain of E. coli resulting
from selection in a continuously growing population.

Selection coefficient (s) = 1-w

where w = relative fitness,
or the rate of survival of
one strain relative to another

In this example
w (strain B) = 0.96
s = 1 - 0.96 = .04
n= # of generations
Heterozygote Superiority
Heterozygote superiority = fitness of
heterozygote is greater than that of both
homozygote and neither allele can be
eliminated by selection

In sickle cell anemia, the allele for

mutant hemoglobin is maintained in
high frequencies in regions of endemic
malaria because heterozygotes are
more resistant to this disease
Random Genetic Drift
• Some changes in allele frequency are random due to
genetic drift, because populations are not infinitely large
Population Bottleneck: population is drastically
reduced by a natural catastrophe or overhunting
In a population bottleneck, only a few individuals are available
to contribute genes to the next generation, thus changing allele
• Elephant seals hunting in 1890s: population → 20
• After hunting ban, population → 30,000
• present-day northern elephant seals almost genetically
Allele frequencies may change by chance in
small populations
Molecular Evolution
Molecular Evolution: The study of how and why gene
sequences change through time constitutes molecular
• Accumulation of sequence differences through time is the
basis of molecular systematics, which analyzes them in
order to infer evolutionary relationships
Molecular Evolution
New genes usually evolve through
duplication and divergence
Orthologs= duplicated in different
species with same function
Paralogs= duplicated in same
species but acquire new or more
specialized function
Pseudogenes = duplicated genes
that have lost their function
Molecular Evolution
A gene tree is a diagram of the inferred ancestral history of a
group of sequences which estimates evolutionary relationships
Neighbor joining = one of the ways to estimate a gene tree
Taxon = the source of each sequence
Molecular Evolution
Synonymous substitution =
no change in amino acid
sequence = primarily at the
third codon position
substitution = amino acid

Rates of evolution of
nucleotide sites differ
according to their function
Molecular Evolution
A gene tree does not always
coincide with a species tree:
 The sorting of
polymorphic alleles in
the different lineages
 Recombination within
gene make it possible
for different parts of the
same gene to have
different evolutionary

A gene tree vs species tree.

Mitochondrial DNA
1. Maternally inherited because the
egg is the major contributor of
cytoplasm to the zygote
2. Human mtDNA evolves at
approximately a constant rate = 1
change per mt lineage every 3800
3. No Recombination, making it a
good genetic marker for human
4. Modern human populations
originated in subsaharan Africa
approximately 100,000 years ago.
Now Solve This
Now Solve This
Probability of Ff mother
q2=1/2500 = 0.0004
q= 0.02 p=0.98, 2pq= 2 (0.02 x 0.98)
2pq = 0.0392 = 98/2500

Probability of Ff Father (The unaffected child of FfxFf) = 2/3

The probability of Ff x Ff giving ff is 1/4