INTRODUCTION

Population genetics is the study of the genetic composition of a population and the forces that determine and change that composition

Let us begin with a few definitions

Species = A group of organisms potentially capable of interbreeding Population = A group of individuals of the same species that exist together in time and space Gene pool = The totality of genetic information possessed by reproductive members of a population

Abert squirrel

Kaibab squirrel

The HARDY-WEINBERG LAW

A mathematical model developed independently in 1908 by Godfrey H. Hardy and Willhelm Weinberg It relates allelic and genotypic frequencies in a population

The HW law has three important aspects 1. Allele frequencies in a population do not change over time 2. Allele frequencies predict genotypic frequencies 3. Equilibrium is achieved in one generation of random mating It disproved the assumption that dominant traits would become more common, while recessive traits would become rarer

The assumptions for the HW law

1. The organisms are diploid and sexually-reproducing 2. The population has a large size 3. Mating within the population is random 4. There is no natural selection 5. There is no mutation or migration

Calculating Allele Frequencies

For a gene with two alleles, the frequency of one allele is designated p , while that of the other allele is designated q p and q do NOT represent the allelic frequencies in an individual, but in the population at large p and q are assigned arbitrarily p + q = 1

Calculating Allele Frequencies

Example = MN blood group in humans

One gene = L Two alleles = LM and LN Three genotypes = LNLN LMLM LMLN

Consider a population of 200 individuals where M = 114 MN = 76 N = 10

Allelic frequencies can be measured in two ways 1) By counting alleles 2) By using genotypic frequencies

Method 1 = Counting Alleles

Frequency of M allele =

# of M alleles

total # of alleles

f(M) = p = [2(114) + 1(76)]/400 304/400 0.76 f(N) = q = [2(10) + 1(76)]/400 96/400 0.24

Method 1 = Counting Alleles

Alternatively, p + q = 1 q = 1 - p q = 1 - 0.76 q = 0.24

Method 2 = Using Genotypic Frequencies

f(MM) = 114/200 = 0.57

f(MN) = 76/200 = 0.38 f(NN) = 10/200 = 0.05

Method 2 = Using Genotypic Frequencies

p = f(M) = f(MM) + (1/2)f(MN) 0.57 + 0.38/2 = 0.76
q = f(N) = f(NN) + (1/2)f(MN) 0.05 + 0.38/2 = 0.24

Calculating Allele Frequencies

Consider a population of individuals segregating the A and a alleles at the A locus What are the possible genotypes of each individual? p = f(A) q = f(a)

Calculating Allele Frequencies

Female Male
A f(A)=p a f(a)=q

A f(A)=p AA
f(AA)=p2

a f(a)=q Aa
f(Aa)=pq

Aa
f(Aa)=pq

aa
f(aa)=q2

Calculating Allele Frequencies

=> The distribution of the three possible genotypes is given by the binomial expansion
(p + q)2

p2 + q2 + 2pq

Hardy-Weinberg Equation
p = allele frequency of one allele q = allele frequency of a second allele p+q=1 p2 + 2pq + q2 = 1 p2 and q2 2pq All of the allele frequencies together equals 1 All of the genotype frequencies together equals 1

Frequencies for each homozygote Frequency for heterozygotes

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NOW consider a population in which the frequency of the A allele is 0.7 and that of the a allele is 0.3 Then p = 0.7 and q = 0.3 Therefore, frequency of genotypes produced by random mating f(AA) = 2 2 p = (0.7) = 0.49 f(Aa) = 2pq = 2(0.7)(0.3) = 0.42 f(aa) = 2 2 q = (0.3) = 0.09

What are the frequencies of alleles in the new generation?

f(A) = f(AA) + (1/2)f(Aa) 0.49 + 0.42/2 0.7 f(a) = f(aa) + (1/2)f(Aa) 0.09 + 0.42/2 0.3

=> Frequencies of the A and a alleles in the new generation are the same as those in the previous generation
Therefore, the population is in HW equilibrium

Important points to consider:

This genetic equilibrium explains why recessive alleles do not disappear When a population is in equilibrium, genetic variability is maintained If any of the assumptions made above are not true, then the population will not be in HW equilibrium

EXTENSIONS OF THE HW LAW

X-linked Genes

Can we still calculate allelic frequencies using HWL? We sure can! First of all, it is easy to calculate frequency of X-linked alleles in males, because it is the same as the phenotypic frequency If we assume identical allele frequencies and random mating, we can use the HW equation to calculate frequency of genotypes in the female

In other words, heres how X-linked traits are handled:

For females, the standard HardyWeinberg equation applies 2 2 p + 2pq + q = 1

However, in males the allele frequency is the phenotypic frequency p + q = 1

Problem In a particular population, the frequency of color blindness in males is 8%. What is the expected frequency in females?

q = 0.08 => Expected f(aa) in females = 2 2 q = (0.08) 0.0064

Multiple Alleles

Example = ABO blood group in humans

One gene = I A B O Three alleles = I ; I ; I A A ; IAIB ; IAIO ; Six genotypes = I I I BI B ; I BI O ; I OI O Four phenotypes = A ; B ; AB ; O

To calculate allelic and genotypic frequencies, we simply add another term to the binomial expansion => p + q + r = 1
p = IA q = IB r = IO

=> genotypes in a population under random mating will be given by 2 (p + q + r) 2 2 2 p + q + r + 2pq + 2pr + 2qr
I AI A IBIB IOIO I AI B I AI O I BI O

Consider a population of 500 individuals

Blood Type A
B AB O

Number
199 53 17 231

f(OO) = 231/500 = 0.462

=> r2 = 0.462 => r = 0.462

= 0.680

Blood types A and O only include genotypes IAIA , IAIO and IOIO => The frequency of A and O phenotypes is given by (p + r)2

The frequency of A and O phenotypes = (199 + 231)/500 = 0.860

Therefore, (p + r)2 = 0.860

=> p + r = 0.860 = 0.927 => p = 0.927 r => p = 0.927 0.680 => p = 0.247

q, the frequency of allele IB , can be obtained by similar logic with blood types B and O or simply from the equation p + q + r = 1 => q = 1 (p + r) => q = 1 0.927 => q = 0.073

We can also use the HWL to calculate heterozygote frequency in a population Example: Albinism In some populations, frequency of albinism is 1/10,000 or 0.0001 2 Therefore, q = 0.0001 => q = 0.0001 => q = 0.01

Since p + q =1 => p = 1 q = 1 0.01 => p = 0.99 Heterozygote frequency = 2pq = 2 (0.99)(0.01) ~ 0.02 So, while albinism is rare (1/10,000), being a carrier is not 1/50

How do we know if a population is in equilibrium?

If the calculated frequencies and the observed frequencies are the same Example:

Genotypic Frequencies MM MN NN

Allelic Frequencies M N

Population

Eskimo

0.835

0.156

0.009

0.913

0.087

Aborigines

0.024

0.304

0.672

0.176

0.824

Are the populations currently in equilibrium? They sure are!

Calculated Frequency
MM MN NN

Observed Frequency
0.835 0.156 0.009

(0.913)2

= 0.833

2(0.913)(0.087) = 0.159 (0.087)2 = 0.008

The same is true for the Aborigine population But what if population is NOT in equilibrium? What if a hypothetical population that was 50% Eskimo and 50% Aborigine was formed on an uninhabited island?

The initial frequencies will be:

Genotypic Frequencies MM MN NN

Allelic Frequencies M N

Population

Eskimo

0.835

0.156

0.009

0.913

0.087

Aborigines

0.024

0.304

0.672

0.176

0.824

Genotypic Frequencies MM MN NN

Allelic Frequencies M N

Population

NEW

0.430

0.230

0.340

0.545

0.455

Calculated Frequency
p2 MM 2pq MN q2 NN

Observed Frequency
0.430

(0.545)2 = 0.297 2(0.545)(0.455) = 0.496 (0.455)2 = 0.207

0.230
0.340

=> population is NOT in equilibrium BUT, if mating is random, population will reach equilibrium in one generation

Note: Hardy-Weinberg equilibrium is rare for protein-encoding genes that seriously affect the phenotype However, it does apply to portions of the genome that do not affect phenotype

These include repeated DNA segments Not subject to natural selection

In natural populations, it is difficult to meet all the assumptions of the HW law When one of the assumptions is not met, the population is in disequilibrium This leads to evolutionary change

WHAT ARE THE FACTORS THAT CAN AFFECT EQUILIBRIUM?

1. 2. 3. 4.

Mutation Migration Nonrandom mating Genetic drift

1. Mutation

It is the source of all new alleles => it provides the raw genetic material upon which evolution acts Mutation rates are too low => in the absence of other forces, particularly selection, mutation is negligible in changing gene frequencies

Mutations occur at random Are generally recessive Can be Neutral Detrimental Beneficial

1. Mutation

Selection eliminates deleterious alleles However, harmful recessive alleles are maintained in heterozygotes and are reintroduced by mutations Genetic load is the collection of recessive deleterious alleles present in a population

2. Migration

Migration usually implies the movement of individuals between populations In population genetics we are interested in the movement of genes, or gene flow

2. Migration

Gene flow has two major effects on a population It introduces new alleles into the population It changes the allelic frequencies in populations There is a larger effect of gene flow with small population sizes

3. Nonrandom Mating

Deviations from random mating occur when the choice of mates is influenced by phenotypic resemblance or genetic relatedness

i. When non-random mating occurs based on phenotype, the population is engaged in assortative mating

Positive assortative mating occurs when individuals with similar phenotypes mate preferentially Negative assortative mating occurs when individuals with dissimilar phenotypes mate preferentially

ii. When non-random mating is based on genotype, inbreeding or outbreeding is in force Inbreeding occurs when the mating individuals are more closely related than mates drawn by chance The most extreme form of inbreeding is

Outbreeding occurs when the mating individuals are less closely related than mates drawn by chance

Said to be inbred
Figure 24.6 A human pedigree containing inbreeding

4. Genetic Drift

Any change in gene frequency in a population due to chance

It is very significant for small populations, but not so important for large ones

Sampling error Large populations produce a large pool of gametes More likely that all possible combinations are generated in the offspring If the population is small, the gametes that unite to form the progeny constitute only a sample from the large pool of gametes => this sample could deviate from the larger pool by chance or error

4. Genetic Drift

All genetic drift is caused by sampling errors, which may arise in several ways in natural populations
i. Small population size Population size remains continuously small over many generations

Small population size increases the probability of homozygosity This increases recessive phenotypes in population Example Amish and Mennonite populations of Pennsylvania marry predominantly within their religious groups Maintain their original small genetic pool Increased incidence of otherwise rare traits

Ellis-van Creveld syndrome Figure 15.6

58

4. Genetic Drift

ii. Founder effect New population established by a small, nonrepresentative sample of a larger population The new colony may have different allele frequencies than the original population It may, by chance, either lack some alleles or have high frequency of others

Example of a founder effect The Dunkers Community Emigrated from Germany to Pennsylvania in the 1720s They remained a small isolated group Some allelic frequencies in the Dunkers differs significantly from the frequencies in the general US population and the German population

Allele Frequencies

Phenotypic Frequencies

Population

IA
0.38

IB
0.03

IO
0.59

A
0.593

B
0.036

AB
0.023

O
0.348

Dunker

USA

0.26

0.04

0.70

0.431

0.058

0.021

0.490

Germany 0.29

0.07

0.64

0.455

0.095

0.041

0.410

iii. Bottleneck Effect Occurs when a population is drastically reduced in size as a result of a disaster Rebounds in population size occur with descendants of limited number of survivors Therefore, new population has a much more restricted gene pool than the large ancestral population

Example of a bottleneck effect

Pingelap atoll in the West. Pacific Ocean

Pingelap atoll
Lagoon

Circa 1780, a typhoon and famine left only 30 survivors

Lengkieki

One of the 9 male survivors was a Chief who was heterozygous for achromatopsia, an autosomal recessive disorder characterized by ocular disturbances and complete inability to see colors

If the Chief was the only carrier => the allele frequency = The current population consists of about 3000 individuals, whose ancestry can be traced to the typhoon survivors About 7 % of the population is color blind from infancy => the allele frequency =

Effects of Genetic Drift

i. Allelic frequencies change over time Sometimes, by chance, allelic frequencies may reach 1.0 , in which case the allele is said to be fixed in the population 0.0 , in which case the allele is said to be lost from the population Which allele will be fixed or lost is a function of the original allelic frequency

In smaller populations, allele frequency fluctuates substantially from generation to generation

In larger populations, allele frequency fluctuates much less

Figure 25.7 A hypothetical simulation of random genetic drift

Effects of Genetic Drift

ii. Divergence of populations away from each other