This short gene starts with the start codon ATG and ends with the stop codon TAA, followed by a piece of the 3′ UTR (the part of the mRNA after the gene, which is not translated). Tap any base of the coding strand, then swap it, insert bases after it, or delete it. The gene is transcribed and translated again after every change.
Newest first. Each change is named by what it does to the gene as it was just before. Undo steps back one change.
Hemoglobin, the oxygen-carrying protein in red blood cells, is made of two alpha-globin and two beta-globin chains. The HBB gene codes for beta-globin. Below is the real start of its coding sequence (codons 1–8 of the human HBB gene, reference sequence NM_000518). Compare the normal gene with the sickle cell allele.
Numbering: modern (HGVS) names count the start methionine as codon 1, so the sickle change is p.Glu7Val; the traditional name Glu6Val (“beta 6”) comes from counting the finished protein, whose first methionine is removed. On each card, the number in brackets is the traditional number.
The most common cystic fibrosis allele deletes three bases from the CFTR gene. Here are codons 507–509.
The CFTR protein that is missing phenylalanine 508 folds badly. Most of it is broken down by the cell before it reaches the cell membrane, where it should work as a channel for chloride ions. Thick, sticky mucus then builds up in the lungs and other organs.
Learn the words for reading a gene and its mutations. Pick Basic (6 labels) or Advanced (9), then try the blank diagram, the label quiz and match the jobs. On a phone, swipe the diagram sideways.
Tap a word, then tap the numbered box it belongs to (on the diagram or in the list below). Tap a filled box to take the word back.
Each line describes the job of one part. Tap a part name, then tap the box next to the job it does. Tap a filled box to take the word back.
Each item is a single mutation of the gene from the Mutation Lab, made by the model. Compare the DNA (and the protein), then pick the type. 8 items per round.
A worksheet with an answer key: label the diagram, transcribe and translate a gene, name six mutations and their effects, work through the sickle cell change, and explain. A codon chart is included.
AP Biology Topic 6.7 asks how changes in DNA change the phenotype, where mutations come from, and why they matter for evolution. Here is the bigger picture.
Only about 1–2% of human DNA codes for protein, but other DNA has jobs too. A change in a promoter or enhancer can change how much mRNA is made, so the cell makes too much or too little of a normal protein. A change at a splice site (the edges of an intron) can make the cell cut the pre-mRNA in the wrong place, so an exon is skipped or part of an intron is kept. Many cases of beta-thalassemia, a blood disorder, are caused by promoter and splice-site mutations in HBB, not by changes to the amino acids.
Even a “silent” change can sometimes matter, for example if it breaks a signal used in splicing or changes how fast that part of the mRNA is translated. Silent means the amino acid is unchanged, not that the change can never have an effect.
A mutation is the change in DNA. A mutagen is something that makes mutations more likely. Some mutations happen with no mutagen at all, as rare copying mistakes during DNA replication.
Cells fix most damage before it becomes a mutation. DNA polymerase proofreads as it copies; mismatch repair fixes wrongly paired bases it misses; excision repair cuts out damaged bases or thymine dimers and fills the gap. Together they make copying extremely accurate: roughly one mistake per billion or so bases copied. People with xeroderma pigmentosum cannot remove thymine dimers well and get skin cancers easily from sunlight.
In eukaryotic cells, an mRNA with an early stop codon is often destroyed (nonsense-mediated decay), so a nonsense mutation may give almost no protein at all.
A somatic mutation happens in a body cell, such as a skin or lung cell. It is copied into that cell’s descendants and can lead to cancer, but it is not passed to children. A germline mutation is in a cell that makes eggs or sperm, so it can be inherited and then is in every cell of the child.
Germline mutations are the original source of new alleles. Most are neutral or harmful, a few are helpful in a given environment, and natural selection acts on this variation. Mutations are random with respect to what the organism needs: they are not caused by the need for them.
These are order-of-magnitude estimates from DNA sequencing studies; real rates vary between people, species, genes and positions in the genome.
About 1.2 × 10−8 is a widely used estimate from sequencing parents and children (for example Kong et al., 2012, Nature 488:471–475); the number per child rises with the father’s age. A diploid human genome has about 6.2 × 109 base pairs.
Uses about 2 × 10−10 mutations per base pair per generation, a rough estimate for E. coli. A flask of bacterial culture can hold 109 cells or more. Classic experiments (Luria & Delbrück, 1943) showed that resistant mutants arise at random before the bacteria meet the virus or drug that selects them.
Read this: THE CAT ATE THE RAT. Change one letter: THE CAT ATE THE HAT. One word is different, but the sentence still reads. Now delete the first T: HEC ATA TET HER AT. Every word after the deletion is nonsense. A gene is read the same way, in three-letter “words” called codons, starting at a fixed point (the start codon).
A substitution (point mutation) swaps one base for another and changes at most one codon. If the new codon still codes for the same amino acid, it is silent: most amino acids have two to six codons, often differing only in the third base. If it codes for a different amino acid, it is missense; how much that matters depends on how different the amino acids are and where they are in the protein. If it becomes a stop codon (UAA, UAG or UGA), it is nonsense, and the protein is cut short.
Inserting or deleting one or two bases changes how every later base is grouped into codons. This is a frameshift: the amino acids after the change are all different, and a stop codon usually turns up soon, because about 3 of every 64 codons are stops. Inserting or deleting three bases (or a multiple of three) keeps the frame: one amino acid is added or lost (an in-frame change), like cystic fibrosis F508del. Changes to the stop codon itself can make the protein longer (stop-loss), and changes to the start codon can stop the protein being made at all.
A protein’s shape comes from its amino acid sequence, and its job comes from its shape. So a mutation can change a trait when it changes the amount, the shape or the timing of a protein. Sickle cell disease shows every level at once: one base pair (DNA) → one amino acid (protein) → sticky hemoglobin fibers (molecules) → sickled red blood cells (cells) → pain and anemia (organism) → but protection against malaria in carriers (population). Whether a mutation is harmful, neutral or helpful depends on the protein and on the environment.
In the Mutation Lab, change the third base of codon 4 (GGT) and see that it is silent. Undo, then change the middle base of codon 5 (GAG to GTG): the same change as in sickle cell. Undo, then delete one base near the start and count how many amino acids change. Finally, delete three bases in a row and compare. Then try all six challenges.
Mutations are behind inherited diseases and cancer, but they are also the raw material of evolution. Some examples:
| Area | How mutations matter |
|---|---|
| Inherited disease | Many genetic disorders are caused by a change in a single gene: sickle cell disease (a missense change in HBB), cystic fibrosis (most often the in-frame deletion F508del in CFTR) and many others. Genetic testing reads these changes directly. |
| Cancer | Cancer usually starts when a cell builds up several somatic mutations in genes that control cell division: some make growth signals stuck “on” (oncogenes), others break the genes that normally stop division or repair DNA (tumor suppressors, such as TP53). UV light and tobacco smoke raise cancer risk by causing mutations. |
| Antibiotic resistance | In a huge population of bacteria, a few cells may by chance carry a mutation that lets them survive a drug. When the drug kills the others, the resistant ones multiply. This is natural selection that we can watch happen. |
| Evolution | New alleles first arise by mutation. Natural selection, genetic drift and gene flow then change how common they are. For example, mutations that keep the lactase enzyme working into adulthood became common in some human populations that kept dairy animals. |
| Viruses and vaccines | Viruses with RNA genomes, such as influenza, mutate quickly. Changes in their surface proteins are one reason the flu vaccine is updated, and why public-health labs sequence viruses to track new variants. |
| Gene editing and medicine | Tools such as CRISPR-Cas9 can make, or correct, a chosen mutation in the lab. Some new treatments for sickle cell disease are based on gene editing. |
Related pages: protein synthesis (translation), transcription, DNA replication, natural selection.
A point mutation is a change at a single base pair of DNA. Most often it means a substitution: one base is swapped for another, such as A for T. Depending on the codon it hits, a substitution can be silent (same amino acid), missense (a different amino acid) or nonsense (a stop codon). Some books also count a single-base insertion or deletion as a point mutation, but those cause frameshifts.
Key takeaway: one base pair changed, usually a substitution.All three are substitutions. In a silent mutation the new codon codes for the same amino acid, so the protein does not change. In a missense mutation the codon codes for a different amino acid, so one amino acid in the protein changes. In a nonsense mutation the codon becomes a stop codon (UAA, UAG or UGA), so the protein is cut short and usually does not work.
Key takeaway: same amino acid, different amino acid, or an early stop.A frameshift mutation is an insertion or deletion of a number of bases that is not a multiple of three. Because codons are read in groups of three from the start codon, the change regroups every base after it into new codons. The amino acids after the mutation are all different, and an early stop codon usually appears, so the protein usually does not work.
Key takeaway: adding or losing 1 or 2 bases regroups every codon after it.A substitution swaps one base for another, so the length of the gene stays the same and at most one codon changes. An insertion adds one or more bases and a deletion removes them. If the number added or removed is not a multiple of three, the reading frame shifts; if it is a multiple of three, amino acids are added or lost but the frame is kept.
Key takeaway: swap, add or remove bases; only adding or removing can shift the frame.No. Many mutations are neutral: they are silent, or they fall in DNA that does not code for protein, or the new amino acid works just as well. Many are harmful, and a few are helpful in a particular environment. The sickle cell allele is harmful in two copies but protects carriers against severe malaria; other mutations let bacteria resist antibiotics or let adults digest milk.
Key takeaway: most are neutral or harmful; a few help, depending on the environment.Some mutations happen naturally, as rare copying mistakes when DNA is replicated, or from chemical changes in DNA that happen on their own. Others are caused by mutagens: UV light (which forms thymine dimers), ionizing radiation such as X-rays, and certain chemicals, for example in tobacco smoke. Cells repair most damage, so only a small fraction becomes permanent mutations.
Key takeaway: copying errors plus mutagens such as UV, radiation and some chemicals.Yes. Sickle cell disease is caused by one base substitution in the beta-globin gene HBB: the codon GAG becomes GTG (GUG in the mRNA), so glutamic acid is replaced by valine. It is a missense mutation, traditionally called Glu6Val; modern HGVS naming, which counts the start methionine, calls it p.Glu7Val. Sickle cell anemia (HbSS) means two copies of this allele; one copy gives sickle cell trait.
Key takeaway: yes: a single missense substitution, GAG to GTG.A somatic mutation happens in a body cell, such as a skin cell. It is passed to that cell’s descendants and can contribute to cancer, but it is not inherited by the person’s children. A germline mutation is in a cell that makes eggs or sperm, so it can be passed on and will then be in every cell of the child.
Key takeaway: only germline mutations are passed to children.First compare the lengths. If bases were added or removed and the number is not a multiple of three, it is a frameshift; if it is a multiple of three, it is an in-frame insertion or deletion. If the length is the same, find the changed codon and look up both the old and new codon in a codon chart: same amino acid means silent, a different amino acid means missense, and a stop codon means nonsense.
Key takeaway: check the length first, then look up the changed codon.Sometimes. A silent mutation does not change the amino acid, so usually it has no effect on the protein. But the same bases can carry other signals: a silent change can disrupt a signal used in splicing the pre-mRNA, or change how quickly that part of the mRNA is translated, which can affect folding. These effects are the exception, not the rule.
Key takeaway: usually no effect, but not never.