Mutations make variation. CRISPR lets us write back. The technology that broke the read-only contract of biology.
Every sub-topic below feeds at least one of these questions.
How do gene mutations occur?
What are the consequences of gene mutation?
The required syllabus content for D1.3, in order. Each card is one lesson-sized checkpoint.
Distinguish between substitutions, insertions and deletions.
Consequences of base substitutions
Specific examples are not required.
Causes of gene mutation
Randomness in mutation
Consequences of mutation in germ cells and somatic cells
Mutation as a source of genetic variation
A gene mutation is a change in the nucleotide sequence of a gene. Three types: substitution, insertion, deletion.
One nucleotide is replaced by another. Affects only that one codon — may or may not change the amino acid.
One or more nucleotides added. If not a multiple of 3, causes a frameshift — all downstream codons changed.
One or more nucleotides removed. Like insertion, usually causes a frameshift if not a multiple of 3.
Whether a substitution affects the protein depends on the degeneracy of the genetic code — many amino acids have multiple codons.
Example — sickle cell anaemia: a single substitution in the β-globin gene (GAG → GTG) changes glutamic acid to valine in haemoglobin. The single amino acid change makes haemoglobin clump together at low O₂, deforming red blood cells into a sickle shape.
Adding or removing bases (not in multiples of three) shifts the reading frame for every codon downstream of the mutation. The protein produced bears no resemblance to the original.
Because codons are read in triplets with no gaps, an insertion or deletion of one or two bases shifts the entire reading frame from that point onward. Every codon downstream is reinterpreted; the protein becomes nonsense and usually non-functional. This is why frameshift mutations are usually worse than substitution mutations.
Mutations have natural causes (replication errors) and external causes (mutagens). They occur at random locations — there's no mechanism for directed mutation.
DNA polymerase makes occasional errors during replication; not all are corrected by proofreading or mismatch repair. Background mutation rate is roughly 10⁻⁹ per base per generation in humans.
Radiation: UV light, X-rays, gamma rays, alpha and beta particles from radioactive decay.
Chemicals: polycyclic aromatic hydrocarbons in tobacco smoke; alkylating agents used in chemotherapy; many industrial pollutants.
They can occur anywhere in the genome (though cytosine has the highest probability of mutating naturally). There is no natural mechanism for directing mutations to a particular base to change a trait. CRISPR-Cas9 is the first technology that gives us deliberate, targeted editing — but it's a human invention, not a natural process.
Mutations in germ cells are inherited; in somatic cells they are not. Either can cause disease — but only germline mutations fuel evolution.
A mutation in a gamete becomes part of the zygote's genome and is inherited by every cell of the offspring. May cause genetic disease (cystic fibrosis, sickle cell anaemia) or, occasionally, beneficial change.
Confined to the individual. But mutations in proto-oncogenes or tumour suppressor genes can cause uncontrolled cell division — cancer.
The bigger picture: mutation is the original source of all genetic variation. Most mutations are neutral (non-coding DNA) or harmful, but the rare beneficial mutation is what natural selection can act on. Without mutation, no evolution.
An extra 3 sub-topics for HL — same syllabus, deeper mechanism.
Gene knockout as a technique for investigating the function of a gene by changing it to make it inoperative
Use of the CRISPR sequences and the enzyme Cas9 in gene editing
Hypotheses to account for conserved or highly conserved sequences in genes
Gene knockout deliberately inactivates a target gene, allowing scientists to determine the gene's function from the resulting phenotype.
The logic is simple: if you remove a gene and see what changes, you can deduce what that gene does. Large libraries of knockout organisms have been created:
CRISPR-Cas9 lets researchers cut DNA at any chosen sequence, enabling precise gene editing. Originally a bacterial defence system; repurposed as a powerful biotechnology.
The system uses two components:
After Cas9 cuts, the cell's own DNA repair machinery rejoins the cut. If a template is provided, scientists can insert or change specific sequences during the repair. This enables precise, targeted editing of any chosen gene.
CRISPR is so powerful that it raises serious ethical questions. Editing germline (heritable) changes in humans is banned in most countries. Different regulatory systems around the world create complications; international efforts aim to harmonise rules around clinical use.
Some gene sequences are nearly identical across all life — they've been preserved by natural selection because mutations are nearly always harmful.
Highly conserved sequences include:
Hypothesis: mutations in these sequences are nearly always lethal, so they don't accumulate in surviving lineages. The fact that we can use these genes for phylogenetic comparisons across all kingdoms is direct evidence of their conservation and shared ancestry.
If you can't define one of these in a sentence, that's where to revise next.
“How can natural selection lead to both a reduction in variation and an increase in biological diversity?”
“How does variation in subunit composition of polymers contribute to function?”