BIOL2410 General Genetics

Genetic variations in
natural populations
Prof. LM Tsang
MSL 106
lmtsang@cuhk.edu.hk
Ext 3057
 Population
• Population is all the members of a
single species occupying a particular
area at the same time and
reproducing with one another.

Hierarchy of biological
Processes occur in natural that affect
organization
population dynamic
Variations within a species
Genetic Variation
• Genetic variation is a measure of the genetic differences that exist
within a population. The genetic variation of an entire species is often
called genetic diversity. These variations are inheritable and will
determine the phenotype & fitness of an individual and population

• Genetic variation is caused by:

1. Mutation
2. Random mating between organisms
3. Random fertilization
4. Crossing over (or recombination)
during meiosis
The last three of these factors reshuffle
alleles within a population, giving offspring
combinations which differ from their
parents and from others.
Genes and phenotypic variations
• Phenotype is controlled by gene (allele)
• No. of phenotypes for a given trait depends on how many genes control
the trait & how many alleles at each locus
• Monogenic trait: controlled by only one gene
• Most traits are controlled by two or more genes and are, polygenic
traits

In these examples, all of the alleles are

incompletely dominant and have additive effects.
 Mendelian explanation of continuous variation
• The more genes or alleles, the more possible phenotypic classes and the
greater the similarity to continuous variation
• The distribution of phenotype will be further smoother by
environmental factors

Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed.,Chapter 3
Human skin color as example of polygenic traits
Major subdivisions of Genetics
• Classical Genetics (傳統遺傳學)
• Describe how traits (physical characteristics) are inherited from
one generation to the other.
• Molecular Genetics (分子遺傳學)
• The study of structures and functions of genes at the molecular
level (i.e. DNA, RNA and proteins)
• Population Genetics (族群遺傳學)
• Apply Mendelian genetics and Darwin’s theory of evolution to
look at the genetic makeup (and changes in makeup) of
population
 Classical Genetics Molecular Genetics

Population Genetics

How different subdivision of Genetics concern about

the issue of human skin color
Chaplin 2004. Geographic distribution of environmental factors influencing human skin
coloration. American Journal of Physical Anthropology, 125, 292–302.
 What is Population Genetics?
• The study of the 1/ distribution of alleles and 2/ change of allele
frequencies (and hence genotype and phenotype frequencies) over
space and time among populations
 Dependent on both Darwin’s theory of natural selection and
Mendel’s laws of inheritance.

Explore the processes and force

for adaptation, speciation, and
population structure in nature
Basic terms & indexes in population genetics
• All of the alleles of all of the genes possessed by all of the members
of the population are contained in the gene pool of the population
• Measuring variation:
1. Allelic frequency: relative frequency of a particular allele in a
population
2. Proportion of heterozygotes and genotype
3. No. of allele and polymorphic loci

Allelic frequency:
Black allele = 40%
Brown allele = 60%

No. of copies of allele A in population

Frequency of allele A = Total no. of copies of alleles in population
Calculation of allelic frequency based on
phenotypic frequency (or vice versa)
• If a population of wildflowers that is
incompletely dominant for color
CR CR  320 red flowers (CRCR)
 160 pink flowers (CRCW)
 20 white flowers (CWCW)
• The number of copies of each allele
CW CW  CR  (320  2)  160  800
 CW  (20  2)  160  200
• Frequency of each allele
 p  freq CR  800 / (800  200)  0.8
CR CW  q  freq CW  200 / (800  200)  0.2
• The sum of alleles is always 1
 0.8  0.2  1
Hardy-Weinberg Equilibrium
• In a population where gametes contribute to the next
generation randomly and Mendelian inheritance occurs,
allele and genotype frequencies remain constant from
generation to generation

• Such a population is in Hardy-Weinberg equilibrium

(HWE)
 Frequencies of alleles
p  frequency of CR allele  0.8

q  frequency of CW allele  0.2

Alleles in the population

Gametes produced
Each egg: Each sperm:

80% 20% 80% 20%

chance chance chance chance
 80% CR (p  0.8) 20% CW (q  0.2)

Sperm
CR p  0.8 CW q  0.2

Punnett square
CR
p  0.8
0.64 (p2) 0.16 (pq)
Eggs CRCR CRCW

CW 0.16 (qp) 0.04 (q2)

q  0.2 CRCW CWCW

64% CRCR, 32% CRCW, and 4% CWCW

Gametes of this generation:

64% CR 16% CR
  80% CR  0.8  p
(from CRCR plants) (from CRCW plants)
4% CW 16% CW
  20% CW  0.2  q
(from CWCW plants) (from CRCW plants)
With random mating, these gametes will result in the same
mix of genotypes in the next generation:

64% CRCR, 32% CRCW, and 4% CWCW plants

Hardy-Weinberg Equation
• Use binomial equation to calculate the genotypic and allele
frequencies of a population under HWE
 p = frequency of dominant allele
 q = frequency of recessive allele
 (p + q) 2 = p2 + 2pq + q2 = 1

 Expected frequency of homozygous dominant = p2

 Expected frequency of homozygous recessive = q2
 Expected frequency of heterozygous = 2pq

 For 3 alleles in a locus,

 p2+q2+r2+2pq+2qr+2pr = (p + q + r) 2 =1

• The Hardy-Weinberg equation describes the genetic makeup we

expect for a population that is not evolving at a particular locus
Assumptions of HWE
• Apply only to diploid organisms reproduce sexually and
exhibit non-overlapping generations
• The following 5 conditions (assumptions) are met:
1. No mutations
2. No migration (gene flow)
3. Random mating
4. Population size is very large
5. No selection
Assumptions of HWE
• These conditions are rarely if ever met
• If allele/genotype frequencies deviate from HWE and
change from one generation to the next
 microevolution

Change with inheritance Over a long time, evolutionary

over several generations processes produces new species
Microevolution Macroevolution
• Individuals do NOT evolve
• As evolution occurs, genotype and phenotype frequencies changes
occur within a population
• Microevolution – small measurable evolutionary changes within a
population from generation to generation
Five mechanisms of microevolution

(c) Non-random mating

Hardy-Weinberg equation is
significant because it tells us
what factors cause evolution.
 Mechanisms of microevolution
1. Mutations
 The raw material for evolutionary
change
• No mutation  no new variations
among members of a population
for natural selection to act on
 Only germ line mutations matters
 Randomness of mutation:
• can be neutral, beneficial or
harmful; whether it happens or
not is not related to how useful
it is
Why is genetic variation important?

global
Population A: variation warming Population A: survive

Population B: no variation Population B: extinction

Sickle cell anemia – due to a point mutation in the haemoglobin gene
2. Gene flow
• Gene flow - movement of alleles among populations by dispersal
• Can increase variation within a population by introducing novel
alleles from another population
• Continued gene flow reduces differences among populations
• Tends to counter the evolutionary effects of mutation, natural
selection, and genetic drift on a population; but can decrease fitness

Dispersal: movement of individuals, does NOT guarantee survival & reproduction.

Gene flow: transfer to genetic materials, MUST survive for sometime
Gene flow will homogenize
difference among population,
barriers to gene flow on the
contrary, lead to independent
evolution and genetic divergence
among populations.
 3. Nonrandom mating
• Selection of mate according to genotype or phenotype (not chance)
• Assortative mating
 Individuals tend to mate with the same phenotype
 Homozygotes increase in frequency
• Sexual selection
 Males compete for the right to reproduce
 Favors characteristics that increase the likelihood of obtaining mates
Not necessarily select for genotype
or phenotype that confers highest
fitness in that environment
 4. Genetic drift
• Changes in the allele frequencies of a gene pool by chance
• Can cause the gene pools of two isolated populations to become dissimilar
• Some alleles are lost and others become fixed

Effect of genetic drift: Genetic drift in a population can lead to the

elimination of an allele from that population by chance.
Stronger effect in small populations
More likely to lose rare alleles
If there is a drastic change (disease, migration or natural catastrophe) in the survival
of a large population, there is little change in the frequency of that population's
alleles. In a smaller population, drastic change can result in loss of an entire allele.
4. Genetic drift: Bottleneck effect
• An extreme case of genetic drift
• Species suffers a near extinction and only a few survivors go on to
produce the next generation
Case study: Human bottleneck

• The human population is

thought to have gone
through a population
bottleneck about 100,000
years ago.

• There is more genetic

variation among
chimpanzees living within
30 miles of each other in
central Africa than there is
in the entire human species.
Case 2: Bottleneck effect followed by
inbreeding depression in Cheetah
Before bottleneck

Inbreeding
Inbreeding depression
Bottleneck
https://evolution.berkeley.edu/evolibrary/news/070701_cheetah
4. Genetic drift:
Founder effect
• Allele frequencies change as a
result of migration of a small
subgroup of a population
• Alleles carried by founders are
dictated by chance alone.
 e.g. No Native Americans have type
B blood

http://anthro.palomar.edu/vary/vary_3.htm
Case study of founder effect:
• Amish are a group descended from 30
Swiss founders who renounced
technological progress.
• One of the founder had genetic
disease which causes short stature,
extra fingers and toes, and heart
defects
• Today about 1 in 200 Amish are
homozygous for this disease, which is
very rare in the larger US population
• Note: effect of inbreeding as well
5. Natural Selection
• Darwin’s mechanism for evolution
• Adaptation of a population to the biotic and abiotic environments
• Most fit individuals survive and reproduce more than others because
they are better adapted
• The genotypes becomes more prevalent in population generation after
generation (population increase in average fitness; NOT
individual!!)
• Leads to change in allele frequency (reduction in allelic diversity by
filtering of less adapted alleles) of population over time
Types of selection

36
Directional selection

• Occurs when an extreme

phenotype is favored
• Can occur when a population is
adapting to a changing environment
 e.g. Industrial melanism
 Drug resistance in bacteria
Industrial melanism: directional selection

Before soot darkened tree trunks, light moths escaped detection of birds and were more
common. After the advent of industry, dark-colored moths became more common as light
moths were detected and eaten. Increase in the frequency of a dark phenotype due to pollution
 Stabilizing selection
• Occurs when an intermediate
phenotype is favored
• Extreme phenotypes selected
against
• Individuals near the average
are favored
• Most common form of
selection because the average
individual is well adapted to its
environment
 Stabilizing selection: size of human baby
• Human babies born with low birth weight are less likely
to survive.
• Babies born too large have difficulty being born.
• Average size babies are selected for.
Disruptive selection
• 2 or more extreme phenotypes are
favored over intermediate phenotype.

Average-sized seeds become less common, and

larger and smaller seeds become more common
Maintenance of genetic variations
 A population always shows some genotypic variations.
 Population with limited variation may not be able to adapt to
changing environmental conditions.

1. Forces creating/maintaining variation constantly at work:

 Mutations, recombination, independent assortment, and
fertilization create new combinations.
 Gene flow
 Multiple sources of selection forces in nature
2. Diploidy and heterozygote
• Only alleles that are expressed are subject to natural selection
• Heterozygotes can protect recessive alleles
• Balanced polymorphism – when natural selection favors
individuals carrying both versions than homozygote of either
version alone, e.g. sickle cell anaemia
Case study: Sickle cell anemia
 Individuals with sickle cell anemia
HbSHbS
 Tend to die early
 Heterozygotes carry the trait
HbSHbA
 Red blood cells only sickle at
low oxygen concentrations

 Ordinarily the normal genotype is

most fit HbAHbA
 Parasite that cause malaria unable to
live in heterozygote red blood cells
 Each of the homozygotes is selected
against and the heterozygote is favored
 Heterozygous advantage
 Malaria and sickle cell anemia

Recessive allele HbS has a

higher frequency in regions in
Africa where malaria is present.
Summary
• Natural selection is the only one of the five agents of microevolution
that consistently works to adapt organisms to their environment.
Summary
Effect on species Effect on genetic
Mechanism
fitness diversity

Mutation

Migration

Nonrandom
mating

Genetic drift

Natural
selection

Please fill in this table with +/-/?

Exercise

CG CG Number of seedlings
Time
(days) Green Green-yellow Yellow
Total
(CGCG) (CGCY) (CYCY)

7 49 111 56 216
CG CY
Q1: At day 7, what is the number of copy of each allele?

Q2: At day 7, what is the frequency of each allele?

CY CY Q3: Does the allele frequency fit expectation under HWE?

Exercise
After 14 days, the seedlings were checked again:
CG CG Number of seedlings
Time
(days) Green Green-yellow Yellow
Total
(CGCG) (CGCY) (CYCY)

7 49 111 56 216
CG CY
21 47 106 20 173

Q4: At day 21, what is the number of copy of each allele?

CY CY Q5: At day 21, what is the frequency of each allele?

Q6: Does the allele frequency fit expectation under HWE?

Q7: What could have happened?