Genetic variants in non-coding DNA and phenotype

Biology · Gene expression

Can the copying even start?

Start at the non-coding DNA just before a gene and pick a route. One question decides everything: can RNA polymerase bind there?

Can RNA polymerase bind? → Is the gene copied?

On Non-coding DNA just before a gene. 2 branches to choose from.

Non-coding DNA is the DNA between genes. Follow both routes from the stretch just before one gene.

From gene to polypeptide

Step through it. Each stage hands over to the next, and the first stage is the one the tree above could switch off.

1. 1The gene is copied into mRNAWhen the cell needs a protein, its gene is activated and copied into mRNA in the nucleus. That copying is called transcription.+
2. 2The mRNA reaches a ribosomeThe mRNA moves to a ribosome in the cytoplasm.+
3. 3Amino acids are joined upAt the ribosome, amino acids are joined in the order coded by the gene. The chain they form is a polypeptide.+

What you need to know

• Only around 1-2% of the human genome is genes; most of it is non-coding DNA, the DNA between genes.
• Gene expression means a gene is copied into mRNA in the nucleus, then used at a ribosome to build a polypeptide.
• Genes are expressed only when the cell needs their protein; the pancreas makes insulin only some of the time.
• Have a goYour pancreas isn't making insulin at this exact moment. Has the insulin gene vanished?

  No. The gene is still there; it just isn't being expressed because the cell doesn't need its protein right now.

  Genes are expressed only when the cell needs their protein, so 'no protein right now' doesn't mean 'no gene'.

• Some non-coding DNA controls whether a gene is expressed.
• It does this by deciding whether RNA polymerase, the enzyme that copies the gene, can bind just before the gene.
• Have a goFinish the sentence: if RNA polymerase can't bind just before a gene, then the gene can't be ____.

  Copied into mRNA.

  RNA polymerase is the enzyme that copies the gene, so without it binding, the copying never starts.

• A genetic variant is a change in the base sequence of DNA; a substitution swaps one base for another.
• If a variant in that non-coding DNA stops RNA polymerase binding, the gene is not copied, so its protein is not made.
• Have a goPut these in cause-and-effect order: the protein is not made / RNA polymerase cannot bind / the gene is not copied.

  RNA polymerase cannot bind, then the gene is not copied, then the protein is not made.

  Each step causes the next: no binding means no copy, and no copy means no protein.

• Without that protein, the phenotype can change, even though the gene's own base sequence is unchanged.
• So a variant outside every gene can still change the phenotype. 'Non-coding' does not mean 'does nothing'.

The big picture

A genetic variant doesn't have to sit inside a gene to matter. Some non-coding DNA controls whether RNA polymerase can bind just before a gene. If a variant stops it binding, the gene isn't copied, its protein isn't made and the phenotype can change, even though the gene itself is unchanged.

⚠ Watch out

Thinking non-coding DNA does nothing, so only a change inside a gene can alter the phenotype. Some non-coding DNA controls whether a gene is copied, so a variant there can change the phenotype too.

Memory hook

Think landing strip. RNA polymerase is the plane, the non-coding DNA before the gene is the runway. Wreck the runway and the gene, perfectly fine, never gets copied.

Check yourself

A friend says: 'If RNA polymerase can't bind before a gene, the protein is made anyway.' What have they got wrong? (Check: without binding there is no mRNA copy, so no protein.)