8.3 Mutations
Key Takeaways
A substitution can be silent (same amino acid, often a third-base change), missense (a different amino acid), or nonsense (an early stop).
An insertion or deletion that is not divisible by three causes a frameshift and usually produces a useless protein downstream.
Chromosomal mutations include deletion, duplication, inversion, and translocation.
Mutations can come from spontaneous copying errors or from mutagens such as some chemicals and radiation. A somatic mutation is not passed through gametes; a germline mutation can be.
A silent mutation still changes the DNA even though the amino acid stays the same. Not every mutation is harmful; some are neutral.
8.3 Mutations
A mutation is a change in the nucleotide sequence of DNA. The change may be one base, a few bases, or a large piece of a chromosome. Copying mistakes and agents from outside the cell can both cause mutations. Cells repair a great deal of damage, so the mutation is the change that remains and can be copied into daughter cells. Some mutations are harmful. Some are neutral, with little or no effect on function. A neutral change is still a mutation because the sequence itself is different.
Three Kinds of Base Substitution
A substitution replaces one base with a different base. The number of nucleotides stays the same, so the reading frame usually stays in register. In a coding region, the consequence depends on how the codon changes.
A silent mutation changes the codon and leaves the amino acid the same. Redundancy in the genetic code makes this common at the third base of a codon. An mRNA codon GGA specifies glycine. Change the DNA so the transcribed codon becomes GGG, and the amino acid is still glycine. The DNA sequence did change. Silence describes the amino acid, not an untouched gene.
A missense mutation changes one codon so that it specifies a different amino acid. The chain is usually still full length. The classic human example is in beta globin, where a glutamate codon in the mRNA, GAG, becomes a valine codon, GUG. One amino acid is replaced. Missense is not an early stop and not a frameshift.
A nonsense mutation turns a codon that specified an amino acid into a stop codon. Suppose the mRNA codon is UCA, which specifies serine. Change one DNA base so that the mRNA codon becomes UAA. UAA does not specify an amino acid, and the polypeptide ends early. That outcome is nonsense, not a silent mutation, because the amino acid result changed. It is not a frameshift, because the number of bases stayed the same and the codon groups stayed in register up to the new stop.
| Substitution | What happens to the codon | What happens to the polypeptide |
|---|---|---|
| Silent | A different codon for the same amino acid, often by a third-base change | The amino acid sequence stays the same, while the DNA sequence changes |
| Missense | A codon for a different amino acid | One amino acid is replaced, and the chain usually keeps its length |
| Nonsense | A sense codon becomes UAA, UAG, or UGA | Translation stops early and the chain is shortened |
Caution
A silent mutation does change the DNA. The amino acid stays the same, which is why the change is called silent. An unchanged polypeptide sequence is not evidence that the gene sequence was left alone.
Frameshifts from Insertion or Deletion
An insertion adds one or more nucleotides. A deletion removes them. The reading frame is the grouping of the message into threes, counted from the start codon. If the number of bases inserted or deleted is not divisible by three, every codon downstream is regrouped. That regrouping is a frameshift. Amino acids after the lesion are usually wrong. A stop codon often appears in the new frame after only a short run of incorrect residues, so the protein downstream of the change is useless.
A one-base insertion shifts the frame. A two-base deletion does the same, because two is not a multiple of three. An insertion or deletion of three bases, or of six, adds or removes whole amino acids and leaves later codons in their original groups. Divide the number of inserted or deleted bases by three. A remainder of zero keeps the frame. A remainder of one or two shifts it.
Chromosomal Mutations
Chromosomal mutations change a large DNA segment. They sit at a different scale from a one-base substitution.
A chromosomal deletion removes a segment, so the genes on it are missing from that chromosome. A duplication leaves an extra copy of a segment. An inversion flips a segment end to end and reverses its order. A translocation moves a segment to another chromosome. In a reciprocal translocation, two chromosomes trade pieces. A break at the junction can interrupt a gene or place it beside a different control region.
A deletion removes material, a duplication adds a copy, an inversion reverses order, and a translocation moves a segment. The name describes the geometry, not the symptom.
Causes, and Which Cells Can Pass a Mutation On
Some mutations are spontaneous. DNA polymerase can insert a wrong base that escapes proofreading. Ordinary chemistry inside the cell can also damage a base without any added mutagen. Deamination can turn cytosine into uracil. Uracil pairs with adenine. If that uracil is used as a template, the new strand receives adenine, and a later round of copying can replace the original cytosine-guanine pair with a thymine-adenine pair. Spontaneous change does not require an outside dose.
Mutagens increase the chance of a sequence change. Some chemicals alter bases directly. Others slip between stacked bases and make insertions or deletions more likely when the strand is copied. Ultraviolet light can covalently join two neighboring thymines into a thymine dimer. If a dimer is copied before repair, the polymerase may insert an incorrect base. Ionizing radiation can break one or both strands of the backbone. Repair pathways fix much of this damage. A mutation is the sequence change that remains and is copied into daughter cells.
Where the mutation sits in the body decides inheritance. A somatic mutation occurs in a body cell. Mitotic daughters of that cell can carry it, and the individual may be affected, but the change is not delivered through eggs or sperm. A germline mutation occurs in a cell of the lineage that produces gametes, so it can enter an egg or a sperm and be inherited by offspring. Passage to offspring depends on that cell lineage.
Harm is not part of the definition. A silent coding change is often neutral. A missense change may be harmful, neutral, or beneficial in a particular environment. Classify the sequence event first, then ask whether gametes can carry it. A silent mutation still changes the DNA even though the amino acid stays the same.
A substitution changes one DNA base so that an mRNA codon which coded for an amino acid becomes UAA. What kind of mutation is this?
A frameshift, because any stop codon regroups every later codon
A chromosomal translocation, because the gene moves to another chromosome
A nonsense mutation, because UAA is a stop and does not code for an amino acid
A silent mutation, because a one-base change never changes the polypeptide
Which change is a frameshift in a coding region?
Deletion of two nucleotides from the coding sequence
A third-base substitution that changes GGA to GGG and still codes for glycine
Inversion of a chromosome segment that reverses gene order but leaves an untouched gene's codons in their original groups
Insertion of three nucleotides that adds one amino acid and leaves later codons in their original groups
Which statement about mutations is correct?
Every mutation harms the organism, so a neutral sequence change is not a mutation.
A mutation in a skin cell is passed to children through gametes.
A silent mutation leaves the DNA sequence unchanged and changes the amino acid instead.
A germline mutation can be inherited, and a silent mutation does change the DNA even though the amino acid stays the same.
Sections you finish are checked off in the contents.