1. Gene Mutations

2. Causes of Mutations
Mutations result from both internal and external factors
Spontaneous Mutations : Those that are a result of natural changes in DNA structure
Induced Mutations : result from changes caused by environmental chemicals or radiation

3. Categories of Mutations
In multicellular organisms there are two broad categories of mutations:
Somatic mutations:
Arise in somatic tissues which do not produce gametes
Germline mutations:
Arise in cells that ultimately produce gametes
These mutations can be passed to future generations

4. There are two basic classes of mutations: somatic mutations and germ-line mutations

5. Types of Gene Mutations
Number of ways to classify gene mutations
Some classification schemes are based on the nature of the phenotypic effect
Base substitutions
Insertions and deletions

6. Base Substitutions Alternation of a single nucleotide in the DNA
Complementary nature of the two DNA strands
When the base of one nucleotide is altered, corresponding nucleotide on the opposite strand will be altered in the next round of replication
Leads to a base-pair substitution

7. Types of Base Substitution
Base substitutions are of two types:
Transition:
A purine is replaced by a different purine or, alternatively a pyrimidine is replaced by a different pyrimidine
Transversion:
A purine is replaced by a pyrimidine or a pyrimidine is replaced by a purine.
Number of possible transversions is twice the number of possible transitions, but transitions usually arise more frequently

8. A transition is the substitution of a purine for a purine or a pyrimidine for a pyrimidine; a transversion is the substitution of a pyrimidine for a purine or a purine for a pyrimidine

9. Insertions and Deletions
Second major class of gene mutations contains insertions and deletions
Addition or the removal of one or more nucleotide pairs
Insertions and deletions are more frequent

10. Insertions and Deletions
Frameshift mutations:
Insertions and deletions often lead to a change in the reading frame of a gene
Sequences that encode proteins may lead to frameshift mutations changes in the reading frame
Frameshift mutations generally have drastic effects on the phenotype
Addition or removal of one or more amino acids may still affect the phenotype
These mutations are called in-frame insertions and deletions

11. Phenotypic Effects of Mutations
The effect of a mutation must be considered with reference to a phenotype against which the mutant can be compared
Forward Mutation: A mutation that alters the wild-type phenotype
Reverse Mutation (a reversion): changes a mutant phenotype back into the wild type

12. Phenotypic Effects of Mutations
Missense Mutation: base substitution that alters a codon in the mRNA, resulting in a different amino acid in the protein
Nonsense Mutation: changes a sense codon (one that specifies an amino acid) into a nonsense codon (one that terminates translation)

13. Phenotypic Effects of Mutations
Silent Mutation: Alters a codon but due to the redundancy of the genetic code, the codon still specifies the same amino acid
Neutral Mutation: is a missense mutation that alters the amino acid sequence of the protein but does not change its function.
It occurs when one amino acid is replaced by another that is chemically similar or when the affected amino acid has little influence on protein function

14. Phenotypic Effects of Mutations
Loss-of-function Mutations: cause the complete or partial absence of normal function.
A loss-of-function mutation so alters the structure of the protein
Gain-of-function Mutation: produces an entirely new trait or it causes a trait to appear inappropriate tissues or at inappropriate times in development

15. Base substitutions can cause (a) missense, (b) nonsense, and (c) silent mutations

16. Phenotypic Effects of Mutations
Conditional mutations: which are expressed only under certain conditions
Lethal Mutations: which cause premature death

18. Phenotypic Effects of Mutations
Suppressor Mutation: is a genetic change that hides or suppresses the effect of another mutation. This type of mutation is distinct from a reverse mutation, in which the mutated site changes back into the original wild-type sequence

19. Relation of forward, reverse, and suppressor mutations

20. Mutation Rates
The frequency with which a gene changes from the wild type to a mutant
Expressed as the number of mutations per biological unit, which may be mutations per cell division, per gamete, or per round of replication