3.9B - 3.10B - Genetic variants and proteins
Higher tier: compare two routes from a DNA variant to a changed characteristic. Use your knowledge of transcription and translation to distinguish changes in protein quantity from changes in protein shape and activity.
3.9B — Non-coding variants change protein quantity
Prerequisite reminder: RNA polymerase transcribes a DNA template into mRNA; ribosomes read the mRNA and tRNA brings amino acids, which join into a polypeptide and fold into a protein. Protein quantity is the number of molecules produced; activity describes what each molecule does.
A genetic variant is a difference in a DNA base sequence at a particular location. A variant can affect a phenotype, but it does not have to. Here, phenotype means an observable characteristic of an organism.
The non-coding DNA in front of a gene does not specify the order of amino acids in that protein. Its role in this model is to provide the control region where RNA polymerase binds. A variant in this region can therefore change how readily RNA polymerase binds.
Consider the two possible directions:
- If RNA polymerase binds less readily, transcription happens less often. Fewer mRNA strands are produced, so fewer molecules of the protein are made.
- If RNA polymerase binds more readily, transcription can happen more often. More mRNA strands are produced, so more molecules of the protein can be made.
If that protein contributes to an observable characteristic, changing its quantity can change the phenotype. The important point is that the coding DNA may be unchanged: each protein molecule can still have the same amino-acid sequence, shape and activity, but the cell makes a different quantity of it.
In the specified causal route:
non-coding variant -> altered RNA-polymerase binding -> altered mRNA quantity -> altered protein quantity -> possible phenotype change
A non-coding control-region variant can change the amount of protein produced without changing the amino-acid sequence of each protein molecule.
3.10B — Coding variants change protein activity
A variant in the coding DNA lies in the part of the gene whose base order is copied into mRNA. It can therefore change an mRNA codon and alter the order of amino acids assembled during translation.
If the amino-acid sequence changes, the polypeptide may fold differently. A different folded shape can change the protein's activity. For an enzyme, for example, an altered active-site shape may make the substrate bind less effectively, so the reaction rate is reduced. A change in protein activity can then affect the organism's phenotype.
The wording can affect matters. A coding-DNA variant does not guarantee a change in amino-acid sequence or protein activity. The required explanation is the route by which such a variant can have an effect:
coding variant -> altered amino-acid sequence -> altered folding or shape -> altered protein activity -> possible phenotype change
The two variant routes can now be compared directly:
| Feature | Variant in non-coding DNA in front of the gene | Variant in coding DNA |
|---|---|---|
| First specified effect | Changes RNA-polymerase binding | Can change the base sequence copied into mRNA |
| Main protein effect | Changes the quantity produced | Can change the amino-acid sequence, folded shape and activity |
| What may remain unchanged | The sequence and activity of each protein molecule | The quantity produced is not the specified first effect |
| Route to phenotype | A different amount of the protein can alter a characteristic | Different protein activity can alter a characteristic |
Do not merge the routes. Saying only that "the protein changes" misses whether the evidence points to quantity or activity.