1. Schematic of Eukaryotic Protein-Coding Locus
5’ UTR
3’ UTR
Intron 1
Intron 2 5’ 3’
Exon 1
Exon 2
Ex 3
GT AG
GT AG
Regulatory
Sequences
Initiation
codon
Stop
codon

2. Point mutations generally arise during DNA synthesis or repair
Error rate of DNA polymerases
and the
Efficiency of DNA repair
are heritable traits.

3. A C G T Nucleotide Substitution Transversion Transition Transition

4. Synonymous Substitution
ATA TGT ATA AAG GCA CTG GTC CTG
Ile Cys Ile Lys Ala Leu Val Leu
I C I K A L V L
ATC TGT ATA AAG GCA CTG GTA CTG
Presumably neutral in effect.

5. Nonsynonymous Substitution
I C I K A L V L
Ile Cys Ile Lys Ala Leu Val Leu
ATA TGT ATA AAG GCA CTG GTC CTG
ATA TGT ATG AAG GCA CAG GTC CTG
Ile Cys Met Lys Ala Gln Val Leu
Maybe deleterious or advantageous effect.

6. Expected relative frequencies of different types of substitution% %
1st Codon position
Synonymous =
Nonsynonymous =
2nd Codon position
Synonymous =
Nonsynonymous = 100 %
3rd Codon position
Synonymous = 69
Nonsynonymous = 31

7. Coding Sequence Mutations vs Regulatory Sequence Mutations
Which are more important in evolution?
5’ UTR
3’ UTR
Intron 1
Intron 2 5’ 3’
Exon 1
Exon 2
Ex 3
GT AG
GT AG
Regulatory
Sequences
Initiation
codon
Stop
codon

8. Hemoglobin
Sickle cell
Anemia
A ---> G
Codon #6,
nucleotide 2

9. Sickle-Cell Anemia: Example of a Structural Point Mutation

10. Evolution of Maize

11. Mutation Rates
Phenotypic method (see Table 8.2):
Counting the number of mutations observed in a laboratory
or field stock.
10 -6 to mutations per gamete per generation
Indirect Sequence method (see Table 8.3):
Average mutation rate per base pair per generation is:
= D / 2 t

12. Evolutionary Implications of Mutation Rates
Human genome = ~6 x 109 bp per diploid genome
If compare human vs chimp sequences:
= 1.3 x / bp (site) / year or
 = 2 x / bp (site) / generation ( yr)
Under these assumptions, the average genome will carry
120 new mutations / generation.
If only 2.5 percent of the genome is transcribed, then
3 mutations will be expressed and might have phenotypic
effects.