BIOL 3301
GENETICS
Date: Monday, April 14, and Wednesday, April 16:1.00-2.30 pm
Chapters 15 and 16
Gene Mutation and Mechanisms of Gene Mutation..
Chapter 15: Gene Mutation.
Mutation: hereditary change
Gene mutation: an allele of a gene changes, becoming a different allele
Chromosome mutation: segments of chromosomes, whole chromosomes, sets of
chromosomes change.
Forward mutation: any change away from the wild-type allele
Reverse mutation (reversion): any change back to the wild-type allele
How DNA Changes affect Phenotype. (Figs. 15-1, 15-2)
Point mutations: alterations of single base pairs of DNA, or to a small number of adjacent
base pairs.
Two main types of point mutations: base substitutions, and base additions/deletions.
Base substitutions:
- transition: Pu->Pu or Py -> Py
- transversion: Pu->Py or Py->Pu
Consequences of different categories of point mutations in coding sequence:
1. Silent substitution: the mutation changes one codon for an amino acid into another
codon for the same amino acid.
2. Missense mutation: the codon for one amino acid is replaced by a codon for another
amino acid
Missense mutations lead to:
Synonymous substitution: the original amino acid is replaced by a chemically similar
amino acid
Non-synonymous substitution: replacement by a chemically different amino acid are
more likely to lead to severe changes in protein structure and function.
-Mutations in or close to the active site of the protein will most likely lead to a lack of
function: such mutations are called null mutations.
-Mutations that are further away from the active site may have less deleterious
effects, often resulting in leaky mutations.
3. Nonsense mutation: the codon for one amino acid is replaced by a translationtermination (stop) codon. This usually leads to the production of an inactive protein.
Single base additions or deletions lead to frameshift mutations.
Mutations that do not affect coding sequences but rather regulatory and other noncoding sequences: e.g. mutations in promoter, operator, Shine-Dalgarno sequence, splicesite, can lead to dramatic effects on gene transcription or protein translation.
Consequently, many of these mutations may be null mutations.
Somatic versus germinal mutation.
A somatic mutation occurs in somatic tissues. A population of identical cells derived
from the cell that mutated in the soma, is called a clone. (Fig. 15-5)
Germinal mutations occur in the germ line, special tissue that is set aside in the course of
development to form sex cells. If such a mutant sex cell participates in fertilization, then
it is passed on to the next generation. (Fig. 15-8)
Mutant types.
Morphological mutations: affect the visible properties of an organism. (Fig. 15-9)
Lethal mutations: affect viability of the organism.
Conditional mutations: cause a mutant phenotype only under restrictive conditions, but
cause a wild-type phenotype under permissive conditions (e.g. temperature sensitive)
Biochemical mutations: are identified by the loss or change of some biochemical function
of the cells, typically resulting in an inability to grow and proliferate.
(e.g. Microorganisms are mostly prototrophic and can exist on a minimal medium
containing only inorganic salts and an energy source. Biochemical mutants often are
auxotrophic, and must be supplied additional nutrients if they are to grow). (Fig. 15-11)
Loss-of-function mutations: or null mutations are usually recessive. However, in some
cases they are dominant. This means that the single remaining wild-type allele is unable
to provide the amount of gene product needed for the cells and the organism to be wild
type.
Gain-of-function mutations: result in a new function added to a gene. The phenotype will
be expressed in the heterozygote. (Fig. 15-12)
Occurrence of mutations.
Mutations are a natural phenomenon.
In modern genetics, mutant genes are used as probes to study biological processes, and to
study the process of mutation itself.
Mutation detection systems: are sets of circumstances in which a mutant allele will
make its presence known at the phenotypic level. This allows for the detection of rare
mutations in large scale searches or screens. Example: Stadler’s specific-locus test. (Fig.
15-13)
How common are mutations ?
-
mutation rate: is the number of mutations occurring in some unit of time
mutations frequency: is the frequency at which a specific kind of mutation is found in
a population of cells or individuals.
Selective systems.
A selective system: is an experimental protocol designed to separate the desired mutant
types from wild-type individuals. Examples: reversion of auxotrophs, filtration
enrichment, resistance of E. coli to T1 phage. (Figs. 15-19, 15-20, 15-21)
Mutagens: are used to increase the mutation rate.
Chapter 16: Mechanisms of Gene Mutation.
Spontaneous mutations.
- errors in DNA replication: transitions, transversions, frameshift (Streisinger model),
deletion and duplication (Figs. 16-1, 16-2, 16-3, 16-4, 16-12)
- spontaneous lesions: depurination, deamination, oxidative damage (e.g. 8-oxodG)
(Figs.16-7, 16-8, 16-10)
Induced mutations.
-mechanism of mutagenesis: incorporation of base analogs (e.g. 5-Bromouracil) , specific
mispairing (e.g. EMS, intercalating agents), loss of specific pairing and the SOS system
(aflatoxin B1, UV) (16-14, 16-15, 16-17, 16-18b,16-20a, 16-21)
Biological repair mechanisms.
- avoid errors before they happen: removal of superoxide radicals by superoxide
dismutase (SOD) and catalase
- direct reversal of damage: photolyase, alkyltransferase (16-25)
- excision repair pathways: general excision repair (excision of an oligonucleotide),
specific excision pathways (DNA glycosylase repair pathway, AP endonuclease repair
pathway, GO system) (16-29, 16-30)
- post-replication repair: mismatch repair, recombinatorial repair, SOS system (16-32)
- repair defects and diseases: e.g. Xeroderma pigmentosum