BIO 140
Lecture 11
Lecture 11
Introduction to Population Genetics:
Genetic Variation
Genetics
•branch of biology concerned with
heredity
and variation
Population Genetics
Population Genetics
•genetics at the population level
•branch of genetics which deals with the
behavior of genes in population
Population Genetics
•the study of polymorphism
and divergence
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BIO 140
Lecture 11
Important topics within population genetics
Genetic Variation
• genetic heterogeneity in a
population
• Genetic structure of populations
• Hardy-Weinberg Equilibrium
• Variation in natural populations
• enables the species to adapt to
future novel changes in the
environment
• Forces that change gene frequencies
• raw material for evolution
• Genetic variation in space and time
• Speciation and the role of genetics in
conservation biology
How is genetic variation measured?
Isozymes
• univariate and multivariate statistics
• functionally similar but separable
forms of enzymes encoded by one
or more loci
• use of isozymes
•use of other genetic markers such
as RAPDs, RFLP, AFLP,
minisatellites, microsatellites,
SNPs, CNVs, DNA sequences of
mtDNA and nuclear markers
Isozyme analysis: monomeric enzyme
Genotype:
FF
SS
FS
Isozyme analysis: dimeric enzyme
Genotype:
FF
SS
FS
Banding
Banding
pattern:
pattern:
= F (fast allele)
= F (fast allele)
= S (slow allele)
= S (slow allele)
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BIO 140
Lecture 11
How are isozymes used to describe
population genetic structure?
Isozyme analysis: tetrameric enzyme
▪ Allele frequency
▪ Average number of alleles per locus
Genotype:
FF
SS
▪ Percentage of polymorphic loci
FS
▪ Individual heterozygosity
Banding
▪ Average heterozygosity over all loci
pattern:
▪ Nei’s genetic distance coefficients
= F (fast allele)
= S (slow allele)
mtDNA markers
Measures of genetic variation using DNA markers
▪2 rRNAs
▪ Polymorphism = % of loci or nucleotide positions
showing more than one allele or base pair.
▪22 tRNAs
▪13 proteins
16 – 17 kb
▪ Heterozygosity (H) = % of individuals that are
heterozygotes.
mtDNA
mitochondrion
Measures of genetic variation using DNA markers
▪ Allele/haplotype diversity = measure of # and
diversity of different alleles/haplotypes within a
population.
▪ Nucleotide diversity = measure of number and
diversity of variable nucleotide positions
within sequences of a population.
Calculating intrapopulation nucleotide diversity
▪ Genetic distance = measure of number of base pair
differences between two homologous sequences.
▪ Synonymous/nonsynonymous substitutions = % of
nucleotide substitutions that do not/do result in amino
acid replacement.
(πX) measures the average weighted
sequence divergence between haplotypes
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BIO 140
Lecture 11
Using sequence data: intrapopulation nucleotide
diversity
Calculating haplotype diversity (H)
• a measure of the frequencies and number of
haplotypes among individuals
• tells about the degree of nucleotide diversity among
several sequences in a given region of the genome
• equivalent to the measure of allelic diversity within a
locus
• ranges from 0 to 1
H=
n 

1 −  xi 2 

n −1 
1

xi = relative haplotype frequency of each haplotype
n = sample size
Calculating intrapopulation haplotype diversity
Interpreting haplotype and nucleotide diversities
Population 1
Large H (≥ 0.5)
Small H (<0.5)
H=
n 

1 −  xi 2 
n − 1 
1

Population 2
f(seq1)=0.2
f(seq2)=0.2
f(seq3)=0.2
f(seq4)=0.3
𝐻𝑃𝑜𝑝𝑢𝑙𝑎𝑡𝑖𝑜𝑛 1 =
10
1 − (0.52 + 0.22 + 0.12 + 0.22)
9
𝐻𝑃𝑜𝑝𝑢𝑙𝑎𝑡𝑖𝑜𝑛 1 = 0.73
10
𝐻
1 − (0.22 + 0.22 + 0.22 + 0.32)
Population 3 𝑃𝑜𝑝𝑢𝑙𝑎𝑡𝑖𝑜𝑛 2 = 9
𝐻
𝑃𝑜𝑝𝑢𝑙𝑎𝑡𝑖𝑜𝑛 2 = 0.88
f(seq1)=0.9
10
f(seq3)=0.1 𝐻
1 − (0.92 + 0.12)
𝑃𝑜𝑝𝑢𝑙𝑎𝑡𝑖𝑜𝑛 3 =
9
𝐻𝑃𝑜𝑝𝑢𝑙𝑎𝑡𝑖𝑜𝑛 3 = 0.2
Calculating allelic frequencies
Calculating allelic frequencies
A hypothetical population consists of 1000 individuals. The
genotypic frequencies for the MN blood typing of the
population are as follows:
frequency
rel. freq.
MM
300
0.3
MN
600
0.6
Compute for the allelic frequencies.
▪ Recent population
▪ Population bottleneck
bottleneck
followed by rapid
Small π
(<0.5%) ▪ Founder event by a
population growth and
single or a few mtDNA
accumulation of
lineages
mutations
▪ Divergence between
▪ Large stable population
geographically
with long evolutionary
Large π
subdivided populations
history
(≥ 0.5%)
▪ Secondary contact
between differentiated
lineages
NN
100
0.1
frequency
rel. freq.
MM
300
0.3
MN
600
0.6
NN
100
0.1
A. Counting the number of each allele
𝑓 𝑀 =𝑝=
𝑓 𝑁 =𝑞=
2 𝑓 ℎ𝑜𝑚𝑜𝑧𝑦𝑔𝑜𝑢𝑠 𝑓𝑜𝑟 𝑀 +𝑓(ℎ𝑒𝑡𝑒𝑟𝑜𝑧𝑦𝑔𝑜𝑡𝑒𝑠) 2 300 +600
2(𝑡𝑜𝑡𝑎𝑙 𝑛𝑜.𝑜𝑓 𝑖𝑛𝑑𝑖𝑣𝑖𝑑𝑢𝑎𝑙𝑠)
=
2(1000)
=0.6
2 𝑓 ℎ𝑜𝑚𝑜𝑧𝑦𝑔𝑜𝑢𝑠 𝑓𝑜𝑟 𝑁 +𝑓(ℎ𝑒𝑡𝑒𝑟𝑜𝑧𝑦𝑔𝑜𝑡𝑒𝑠) 2 100 +600
2(𝑡𝑜𝑡𝑎𝑙 𝑛𝑜.𝑜𝑓 𝑖𝑛𝑑𝑖𝑣𝑖𝑑𝑢𝑎𝑙𝑠)
=
2(1000)
=0.4
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BIO 140
Lecture 11
Calculating allelic frequencies
frequency
rel. freq.
MM
300
0.3
MN
600
0.6
Calculating allelic frequencies
NN
100
0.1
frequency
rel. freq.
A. Using relative genotypic frequencies
𝑓 𝑀 =𝑝=
=
2(1000)
=0.6
(2)𝑓 ℎ𝑜𝑚𝑜𝑧𝑦𝑔𝑜𝑢𝑠 𝑓𝑜𝑟 𝑀
𝑓(ℎ𝑒𝑡𝑒𝑟𝑜𝑧𝑦𝑔𝑜𝑡𝑒𝑠)
𝑓 𝑀 =𝑝=
+
2(𝑡𝑜𝑡𝑎𝑙 𝑛𝑜. 𝑜𝑓 𝑖𝑛𝑑𝑖𝑣𝑖𝑑𝑢𝑎𝑙𝑠) 2(𝑡𝑜𝑡𝑎𝑙 𝑛𝑜. 𝑜𝑓 𝑖𝑛𝑑𝑖𝑣𝑖𝑑𝑢𝑎𝑙𝑠)
𝑓 𝑀 =𝑝=
MN
600
0.6
NN
100
0.1
A. Using relative genotypic frequencies
2 𝑓 ℎ𝑜𝑚𝑜𝑧𝑦𝑔𝑜𝑢𝑠 𝑓𝑜𝑟 𝑀 +𝑓(ℎ𝑒𝑡𝑒𝑟𝑜𝑧𝑦𝑔𝑜𝑡𝑒𝑠) 2 300 +600
2(𝑡𝑜𝑡𝑎𝑙 𝑛𝑜.𝑜𝑓 𝑖𝑛𝑑𝑖𝑣𝑖𝑑𝑢𝑎𝑙𝑠)
MM
300
0.3
𝑓 ℎ𝑜𝑚𝑜𝑧𝑦𝑔𝑜𝑢𝑠 𝑓𝑜𝑟 𝑀
1
𝑓(ℎ𝑒𝑡𝑒𝑟𝑜𝑧𝑦𝑔𝑜𝑡𝑒𝑠)
+
𝑡𝑜𝑡𝑎𝑙 𝑛𝑜. 𝑜𝑓 𝑖𝑛𝑑𝑖𝑣𝑖𝑑𝑢𝑎𝑙𝑠 2 (𝑡𝑜𝑡𝑎𝑙 𝑛𝑜. 𝑜𝑓 𝑖𝑛𝑑𝑖𝑣𝑖𝑑𝑢𝑎𝑙𝑠)
1
𝑓 𝑀 = 𝑝 = 𝑟𝑒𝑙. 𝑓𝑟𝑒𝑞. 𝑜𝑓 ℎ𝑜𝑚𝑜𝑧𝑦𝑔𝑜𝑢𝑠 𝑓𝑜𝑟 𝑀 + 𝑟𝑒𝑙. 𝑓𝑟𝑒𝑞. 𝑜𝑓 ℎ𝑒𝑡𝑒𝑟𝑜𝑧𝑦𝑔𝑜𝑡𝑒𝑠
2
1
𝑓 𝑀 = 𝑝 = 0.3 + 0.6 = 0.6
2
𝑓 𝑁 =𝑞=
2 𝑓 ℎ𝑜𝑚𝑜𝑧𝑦𝑔𝑜𝑢𝑠 𝑓𝑜𝑟 𝑁 +𝑓(ℎ𝑒𝑡𝑒𝑟𝑜𝑧𝑦𝑔𝑜𝑡𝑒𝑠) 2 100 +600
2(𝑡𝑜𝑡𝑎𝑙 𝑛𝑜.𝑜𝑓 𝑖𝑛𝑑𝑖𝑣𝑖𝑑𝑢𝑎𝑙𝑠)
=
2(1000)
=0.4
(2)𝑓 ℎ𝑜𝑚𝑜𝑧𝑦𝑔𝑜𝑢𝑠 𝑓𝑜𝑟 𝑁
𝑓(ℎ𝑒𝑡𝑒𝑟𝑜𝑧𝑦𝑔𝑜𝑡𝑒𝑠)
𝑓 𝑁 =𝑞=
+
2(𝑡𝑜𝑡𝑎𝑙 𝑛𝑜. 𝑜𝑓 𝑖𝑛𝑑𝑖𝑣𝑖𝑑𝑢𝑎𝑙𝑠) 2(𝑡𝑜𝑡𝑎𝑙 𝑛𝑜. 𝑜𝑓 𝑖𝑛𝑑𝑖𝑣𝑖𝑑𝑢𝑎𝑙𝑠)
𝑓 𝑁 =𝑞=
𝑓 ℎ𝑜𝑚𝑜𝑧𝑦𝑔𝑜𝑢𝑠 𝑓𝑜𝑟 𝑁
1
𝑓(ℎ𝑒𝑡𝑒𝑟𝑜𝑧𝑦𝑔𝑜𝑡𝑒𝑠)
+
𝑡𝑜𝑡𝑎𝑙 𝑛𝑜. 𝑜𝑓 𝑖𝑛𝑑𝑖𝑣𝑖𝑑𝑢𝑎𝑙𝑠 2 (𝑡𝑜𝑡𝑎𝑙 𝑛𝑜. 𝑜𝑓 𝑖𝑛𝑑𝑖𝑣𝑖𝑑𝑢𝑎𝑙𝑠)
1
𝑓 𝑁 = 𝑞 = 𝑟𝑒𝑙. 𝑓𝑟𝑒𝑞. 𝑜𝑓 ℎ𝑜𝑚𝑜𝑧𝑦𝑔𝑜𝑢𝑠 𝑓𝑜𝑟 𝑁 + 𝑟𝑒𝑙. 𝑓𝑟𝑒𝑞. 𝑜𝑓 ℎ𝑒𝑡𝑒𝑟𝑜𝑧𝑦𝑔𝑜𝑡𝑒𝑠
2
1
0.6 = 0.4
𝑓 𝑁 = 𝑞 = 0.1 +
2
5