SUBJECT 4: MUTATION AND REPAIR
INSTABILITY OF THE GENOME
- The genomes are subject to changes in their sequence.
- Genomes are very unstable.
- A mutation is one change in the sequence of DNA that is passed on to
offspring.
- Sequence changes (mutations) can be due tocauses endogenous (spontaneous,(
replication errors, repair errors, ROS) and exogenous agents
physical, chemical, or biological extracellular).
- Mutations, together with meiotic recombination, are the main cause of genetic
variability and, consequently, of theevolution of species through
natural selection → positive effect.
- They can have negative effects (pathologies or predisposition to suffer).
The agencies also have repair mechanisms in place to prevent these errors.
There is a balance between DNA damage and repair. If there is an imbalance, the DNA of
the species experiences damage that can lead to mutations.
CLASSIFICATION OF MUTATIONS
Mutations can occur in somatic cells or germ cells.
- If the mutation affectscells somatic, it is only transmitted to the descending cells in
mitosis, but not to the whole organism (theyare never inherited), giving rise to
mosaics. They are the most common.
- If the mutation occurs in a germ cell (gametogenesis) and does not affect the ability
to reproduce, it will be transmitted separately from the offspring. They are uncommon
(10-6 per locus and cell division).
Depending on when the mutation takes place, it will affect more or less cells. The sooner the
mutation takes place, the more cells will be affected. In other words, if the mutations in germ
cells occur in the early stages of the baby's formation, the baby is severely affected.
, Conversely, if they occur in late stages, the individual will be said to be a mosaic, as it will
be made up of a low proportion of mutated cells.
CLASSIFICATION OF MUTATIONS
mutations Large-scale: chromosomal duplications, deletions, or regroupings (chromosomal
abnormalities).
mutations Small-scale: affect one (point) or more base pairs.
- Deletions: punctual or of a few nucleotides.
- Insertions: punctual, repeated expansions of triplets, transposable elements, tandem
duplications.
- Substitutions: one or multiple (infrequent) bases
- Transversions: purine by pyrimidine or vice versa.
- Transitions: purine by purine or pyrimidine by pyrimidine.
EFFECTS OF
Silentmutations: they do not generate changes in the phenotype (neutral).
- Change of the third nucleotide of a codon (without mutation): The genetic code is
universal and degenerate, that is, there are several amino acids encoded by triplets
of different nucleotides (codon). Therefore, if a mutation occurs in the third nucleotide
of the codon and the triplet synthesizes the same amino acid, there will be no
mutation.
- Mutations in:
- Introns (do not code for mutation)
- Non-coding
- regions Non-regulatory regions.
Non-silent / noisy: they generate changes in the phenotype, which can be harmful or
beneficial (<1%). The consequences can be:
- altered sense mutation(mutationmissence):cANVI a different amino acid for
another. For example: Tre per Cys.
- Nonsense mutation(nonsensemutation)finalització premature STOP codon.
Appearance of a stop codon (STOP), which causes the synthesis of a protein to stop
and, consequently, its inactivation.
→ Proteins always start with methionine (AUG).
INSTABILITY OF THE GENOME
- The genomes are subject to changes in their sequence.
- Genomes are very unstable.
- A mutation is one change in the sequence of DNA that is passed on to
offspring.
- Sequence changes (mutations) can be due tocauses endogenous (spontaneous,(
replication errors, repair errors, ROS) and exogenous agents
physical, chemical, or biological extracellular).
- Mutations, together with meiotic recombination, are the main cause of genetic
variability and, consequently, of theevolution of species through
natural selection → positive effect.
- They can have negative effects (pathologies or predisposition to suffer).
The agencies also have repair mechanisms in place to prevent these errors.
There is a balance between DNA damage and repair. If there is an imbalance, the DNA of
the species experiences damage that can lead to mutations.
CLASSIFICATION OF MUTATIONS
Mutations can occur in somatic cells or germ cells.
- If the mutation affectscells somatic, it is only transmitted to the descending cells in
mitosis, but not to the whole organism (theyare never inherited), giving rise to
mosaics. They are the most common.
- If the mutation occurs in a germ cell (gametogenesis) and does not affect the ability
to reproduce, it will be transmitted separately from the offspring. They are uncommon
(10-6 per locus and cell division).
Depending on when the mutation takes place, it will affect more or less cells. The sooner the
mutation takes place, the more cells will be affected. In other words, if the mutations in germ
cells occur in the early stages of the baby's formation, the baby is severely affected.
, Conversely, if they occur in late stages, the individual will be said to be a mosaic, as it will
be made up of a low proportion of mutated cells.
CLASSIFICATION OF MUTATIONS
mutations Large-scale: chromosomal duplications, deletions, or regroupings (chromosomal
abnormalities).
mutations Small-scale: affect one (point) or more base pairs.
- Deletions: punctual or of a few nucleotides.
- Insertions: punctual, repeated expansions of triplets, transposable elements, tandem
duplications.
- Substitutions: one or multiple (infrequent) bases
- Transversions: purine by pyrimidine or vice versa.
- Transitions: purine by purine or pyrimidine by pyrimidine.
EFFECTS OF
Silentmutations: they do not generate changes in the phenotype (neutral).
- Change of the third nucleotide of a codon (without mutation): The genetic code is
universal and degenerate, that is, there are several amino acids encoded by triplets
of different nucleotides (codon). Therefore, if a mutation occurs in the third nucleotide
of the codon and the triplet synthesizes the same amino acid, there will be no
mutation.
- Mutations in:
- Introns (do not code for mutation)
- Non-coding
- regions Non-regulatory regions.
Non-silent / noisy: they generate changes in the phenotype, which can be harmful or
beneficial (<1%). The consequences can be:
- altered sense mutation(mutationmissence):cANVI a different amino acid for
another. For example: Tre per Cys.
- Nonsense mutation(nonsensemutation)finalització premature STOP codon.
Appearance of a stop codon (STOP), which causes the synthesis of a protein to stop
and, consequently, its inactivation.
→ Proteins always start with methionine (AUG).
