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
Point mutations generally arise during DNA synthesis or repair Error rate of DNA polymerases and the Efficiency of DNA repair are heritable traits.
A C G T Nucleotide Substitution Transversion Transition Transition
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.
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.
Expected relative frequencies of different types of substitution % % 1st Codon position Synonymous = 4 Nonsynonymous = 96 2nd Codon position Synonymous = 0 Nonsynonymous = 100 % 3rd Codon position Synonymous = 69 Nonsynonymous = 31
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
Hemoglobin Sickle cell Anemia A ---> G Codon #6, nucleotide 2
Sickle-Cell Anemia: Example of a Structural Point Mutation
Evolution of Maize
Mutation Rates Phenotypic method (see Table 8.2): Counting the number of mutations observed in a laboratory or field stock. 10 -6 to 10 -5 mutations per gamete per generation Indirect Sequence method (see Table 8.3): Average mutation rate per base pair per generation is: = D / 2 t
Evolutionary Implications of Mutation Rates Human genome = ~6 x 109 bp per diploid genome If compare human vs chimp sequences: = 1.3 x 10 -9 / bp (site) / year or = 2 x 10 -9 / bp (site) / generation (15 -20 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.