Mutations Flashcards
Mutation
Changes in the DNA that replace, insert, or delete nucleotides
Mutations are the ultimate source of…
All new genes and the genetic diversity of life
2 main categories of mutations
1) Large Scale
2) Small Scale
Large Scale Mutations
Affect long segments of DNA
(chromosomal rearrangement)
Small Scale Mutations
Affect one or a few nucleotide pairs
Mutations can alter phenotypes by…
Impacting gene product sequence or expression
–> Altering levels of mRNA + proteins or the STRUCTURE of these molecules
Mutations in Non-Coding Regions of DNA
Don’t impact structure/function of gene products but instead alter gene expression and regulation
Most mutations are within the…
Non-coding region of DNA
Germ Cell Mutations
Inherited between generations
Somatic Cell Mutations
Not inherited
–> But can cause serious problems for people when cells with a mutation proliferate (= cancer)
What factors determine phenotypic effect of a mutation?
1) The type of cell
2) When in the life cycle the mutation occurs (the earlier the more severe its effects)
3) The dominance of a mutation
Point mutations
Changes in a single nucleotide pair of a gene (single base pair change)
2 main types of point mutations:
1) Substitutions
2) Deletions/Insertions
Substitution Mutations
The replacement of one nucleotide and its partner with another pair of nucleotides
Types of substitution mutations
1) Missense
2) Nonsense
3) Silent
Missense Mutations
Change of ONE codon for another which results in a change in the amino acid
–> Causes change in a SINGLE POINT!!!
SUBSTITUTIONS
Mutation in Sickle Cell Anemia
Missense mutation (in hemoglobin)
(A shift from an “a” to a “t”)
Wild type cells = Produce glutamic acid (- charge) at that position
Mutated cells = Produce VALINE (neutral charge) at that position
–> **Replacement of glutamic acid with valine
In sickle cell anemia, what leads to the formation of sickled cells?
The change in the charge of hemoglobin thanks to the replacement (substitution) of glutamic acid (+) by valine (neutral) affects its STRUCTURE
–> Hb forms needle like aggregates within RBCs, giving them their sickled shape
Nonsense Mutation
PREMATURE STOP CODON –> Termination of polypeptide happens earlier than it should
How does a nonsense mutation impact the final polypeptide product?
It shortens it
–> the resulting polypeptide will be shorter and incomplete
Severity of the effect of a nonsense mutation is dependent upon:
Where(“/when”) in the sequence the mutation occurs
–> At the end = almost entire protein is produced normally (less severe)
–> At the beginning = almost no protein is produced (more severe)
Silent Mutations
Substitutions that have no effect on amino acid sequence!
Why are silent mutations possible?
Redundancy of the genetic code (multiple codons call for the same amino acid)
Although silent mutations don’t have protein sequence, they can still have an effect on phenotype if…
The codon change alters “translation efficiency”
–> Most organisms have “codon bias” and are used to dealing with specific codons for amino acids
–> Can affect rate of translation if the new codon is not “preferred” by the cell
Insertions/Deletions
Additions or deletions of nucleotide pairs in a gene
What do insertions and deletions alter?
The reading frame
Frameshift mutations occur when there is…
An insertion or deletion of a number of nucleotides that is NOT divisible by 3
What regions of a protein are altered by insertions and deletions that are frame shifting?
Protein sequence DOWNSTREAM the insertion or deletion will be different from the original protein
Severity of insertions/deletions depends on…
Where in the sequence the mutation occurs
–> Closer to beginning = more incorrectly read AAs = greater severity
Insertion and deletions cause…
Frameshift
Insertions and deletions ARE NOT ______________ mutations
but instead are _________________ mutations
1) Are NOT nonsense or missense mutations
2) ARE FRAMESHIFT mutations
