Gene Frequency, Gene Equilibrium, Hardy-Weinberg principle (law)
Population= a group of sexually interbreeding individuals
Gene frequency (allele frequency)=proportion of all alleles that are of the specific type
Genotype frequency= Proportion of organisms that have the particular genotype
In population, alleles follow the Mendelian principle
Gene pool=sum total of genes in the reproductive gametes of a population
Frequencies of genes in a new generation hinges on frequencies of genes in the previous
generation,
Gene frequencies rather than genes are inherited
Calculation of Genotype Frequency (diploid have 2 alleles for autosomal genes):
MN blood group
50 MM, 20 MN, 30 NN individuals=100 total individuals
Frequency of three genotypes:
MM= 50/100=0.5
MN=20/100=0.2
NN= 30/100=0.3
Sum total of freq of all genotypes=1
Allele frequency=Observed number of each allele/total number of alleles
Allele freq M= 100 alleles from MM individuals+ 20 from MN / 200 total alleles
=120/200=0.6
Allele freq N= 60 from NN + 20 from MN / 200
=80/200=0.4
Allele freq N=1-M
Allele freq M=1-N
Sum total of freq of both alleles=1
Another way of calculation
Freq of an allele=freq of homozygotes for that allele+1/2 freq of heterozygotes for that allele
Freq of M allele= 0.5+1/2(0.2)= 0.6
Freq of N allele=0.3+1/2(0.2)=0.4
Conservation of gene (allele) frequencies through generation
Discovered by Hardy & Weinberg independently
In a population with Taster (for phenylthiocarbonate/ PTC: very bitter taste) & Non-taster
Caused by dominant Taster (allele T ), recessive Non-Taster (allele t)
Three genotypes: TT, Tt, tt
Two phenotypes” Taster (TT and Tt), non-taster(tt)
Suppose initial frequencies of three genotypes in a population are: 0.40TT:0.40Tt:0.20tt
What will be the frequency of these genes after many generation (after one generation)?
The frequency of T= 0.4+0.2=0.6
t=0.2+0.2=0.4
Sum total of all genotype freq=1
If there is random mating (panmixing): 9 different types of matings (3 reciprocals)
Total 6 types of matings
Initial frequencies of three genotypes in the population are: 0.40TT:0.40Tt:0.20tt
After 1 generation: Genotype frequencies: 0.36TT:0.48Tt:0.16tt
(Genotype frequencies changes)
What are the Gene (allele) frequencies?
Freq of T : 0.36+1/2 (0.48)=).36+0.24=0.60
Freq of t: 0.16tt+1/2(0.48)=0.16+0.24=0.40
Allele Frequencies did not change from one generation to next generation, although
Genotype Frequencies changed>> same will follow to another generation
No matter what were the initial frequencies freq of parental genotypes, allele frequencies
do not change generation after generation
=Hardy-Weinberg principle (law): population (equilibrium) will be in equilibrium
All three genotypes in an equilibrium
HWP works under following assumptions:
1. Mating is random: there are no subpopulation
2. Allele frequencies same in males & females
3. All the genotypes are equal in survival and fertility (selection does not operate)
4. Mutation does not occur
5. Migration into the population absent
6. Population is sufficient large
Relationship between Gene Frequencies and Genotype Frequencies in Algebraic term:
p+q=1
Expansion of the binomial (p+q)2=p2+2pq+q2=1
p=freq of a gene, T
q= freq of its allele, t (if there are no other allele)
p+q=1=0.6+0.4=1
p2 (TT)
q2 (tt)
2pq (Tt)
p=0.6, q=0.4
p2=0.36
2pq=2x0.6x0.4=0.48
q2=0.16
Total 1, sum of all genotype frequencies
Allele and Genotype Frequencies for Sex-linked Genes
Males XY; females XX (Five possible genotypes in males & females)
(Only 3 genotypes for autosomal genes)
In females:
p2 (AA):2pq (Aa):q2(aa)
In males (hemizygous):
p(A):q(a) Only two genotypes (genotype frequency=allele frequency)
Q1: An AR disorder affects 1/10,000 individuals.
What is the frequency of mutant allele?
What is frequency of heterozygotes?
q2 genotype aa = 1/10,000
q = 1/100 mutant allele frequency
p = 1-q = 1-1/100 = 99/100 = 1
Heterozygote genotype = Aa
Frequency of heterozygote (carrier)= 2pq = 2 x 1 x 1/100 = 1/50
Q2: X-linked recessive color blindness affects 1/10 males.
What will be the proportion of females affected?
What will be the proportion of the females carriers for the mutant allele?
In males, ‘q’ is the frequency of mutant allele ‘a’ and genotype ‘a’
q=1/10
p=9/10
In females, affected will have genotype ‘aa’ with frequency q2
q2=1/10x1/10=1/100
Carrier females genotype=2pq=2x9/10x1/10=18/100
Q3. Which of the following genotype frequencies of AA, Aa and aa, respectively, satisfy
the Hardy-Weinberg principle?
(a) 0.70, 0.21, 0.09
(b) 0.33, 0.34, 0.33
(c) 0.32, 0.64, 0.04
(d) 0.64, 0.32, 0.04
p=0.8 for allele A
q=0.2 for allele a
Changes in Gene Frequencies
Mutation
Migration
Selection
Heterozygous advantage
Genetic drift
Mutation:
Weak force for changing gene frequencies, mutation rate is low
Newly arised mutation deleterious > eliminated
Newly arised mutation selectively neutral: does not affect the ability to survive and reproduce
>>change gene frequencies
Migration:
New alleles introduced into the population from another population
Natural selection:
Consequence of hereditary differences among organisms in their ability to survive and
reproduce in prevailing environment
Allele which enhances survival & reproductive fitness increase in freq from
generation to generation
Heterozygous advantage: heterozygote is superior genotype
•Scenario 1
•Heterozygote is equal to homozygote in fitness (dominance)
•Heterozygote is intermediate between both types of homozygotes (semi-dominance)
>>Allele associated with superior homozygotes becomes fixed
•Scenario 2
• Fitness of the heterozygotes is superior to either homozygotes>>heterozygotes
produce more offsprings than the homozygotes>>selection of heterozygotes keeps
both alleles in population (even if the allele is deleterious)
e.g., Sickle cell hemoglobin mutation (Hbs) and Plasmodium falciparum malaria in
Africa and Middle East {6th codon in beta-globin (5’-GAG’-3’) Glu> (5’-GUG-3’)Val}
Hbs/Hbs lethal in the absence of any medical care: Hbs Allele freq still high 10%
Hbs/Hb+, sickle cell trait (carrier)- low oxygen in air (mountain climbing), high pressure in
atmosphere (scuba diving), high altitude (flying): 1/12 African American- cause symptoms-pain
& sudden death
Reason: Heterozygotes less susceptible to malaria/sickle-cell trait gives protection against malaria
Heterozygotes have higher fitness
Both alleles present in the population
Normal RBC
Sickle cell
Genetic drift:
• When population becomes small (finite)
• Causes differences in allele freq
• e.g., Computer simulation of 8 adults
with Aa genotypes after many generations
in 12 hypothetical subpopulations
Every generation 16 gametes chosen from
previous generation
A=a=0.5
Combined 12 subpopulations,
Freq of A allele remains ~0.5
Consequence of Genetic Drift for allele frequency
A particular allele gets fixed after certain number of generations
e.g., Allele ‘A’ fixed in some subpopulations
If random genetic drift is the only force at work, alleles would become either fixed
or lost , and there would be no polymorphism
