IB BIOLOGY · THEME D · CONTINUITY AND CHANGE

From one gene to one protein

Every protein you make starts as a message copied from one gene. Here is how a cell copies it, reads it three letters at a time and strings the chain that becomes a working protein, and what one wrong letter can do.

IB Biology D1.2SL and HL3 hours SL, 6 HL12 chapters

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One geneOne messageOne protein
One gene, one message, one protein: a gene is copied into RNA, a ribosome reads the copy, and the chain it builds folds into a working protein.

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Twelve chapters, the last five for higher level. Read one, play or tap its figure, make each prediction before you open the answer, and run the protein factory after chapter 7.

  1. 1Copying a gene into RNA
  2. 2Read for a lifetime, read when needed
  3. 3Three kinds of RNA build a protein
  4. 4Codon meets anticodon
  5. 5A code written in threes
  6. 6One codon at a time
  7. 7One base, one amino acid
  8. 8Five prime to three prime, both times HL
  9. 9Where a gene starts, and DNA that codes for nothing HL
  10. 10Capped, cut and tailed HL
  11. 11Starting the chain HL
  12. 12Finished, then recycled HL

D1.2.1 D1.2.2 Transcription

Copying a gene into RNA

A gene is a stretch of DNA whose base sequence codes for a polypeptide. Proteins are not built where the DNA is kept, so the cell first makes a working copy of the gene in RNA. Making RNA with a DNA template is transcription, and the RNA that carries a gene's message to the ribosomes is messenger RNA (mRNA). In a eukaryotic cell this happens in the nucleus; in a prokaryote, in the cytoplasm.

One enzyme does the whole job. RNA polymerase binds at the start of a gene and parts the two DNA strands over a short stretch (it needs no helicase: that enzyme unzips DNA when the whole molecule is copied, in D1.1). Free RNA nucleotides pair with the exposed bases of one strand only, the template strand. The other strand is the coding strand, because the RNA ends up with its sequence. (You may meet them called antisense and sense.) The enzyme joins each new nucleotide to the last with a covalent bond, moves on, and lets go at the end of the gene.

Complementary base pairing chooses every RNA base. A on the template takes uracil (U), T takes A, C takes G and G takes C. The pairs are held by hydrogen bonds: weak enough to form and break as the enzyme passes, but specific, because only the right base fits. That is how the sequence is copied exactly. Behind the enzyme the RNA peels away and the DNA strands pair up again.

  • The RNA is complementary to the template, and has the same sequence as the coding strand, with U where DNA has T.
  • Only the template is read. The coding strand takes no part.

Which way the RNA grows is chapter 8, and how the enzyme finds the start of a gene is chapter 9.

Remember it Which base pairs with which in transcription

  • ApplesA on the templatepairs with U in the RNA
  • UnderU in the RNAuracil, where DNA has T
  • CarsC on the templatepairs with G in the RNA
  • GarageG on the templatepairs with C in the RNA
Watch out RNA polymerase, not helicase, parts the DNA in transcription. And the RNA is not a copy of the template: it is complementary to it, and matches the coding strand (with U for T).

A gene's template strand reads T A C C T G. Which RNA does RNA polymerase make from it?

RNApolymeraseAHAHCHCHGHGHTHTHGHGHCHCHAHCHGHTHGHCHTHGHCHAHCHGHAOHCOHGOHUOHAOHCOHGOHCOHGOHUOHGOHCOHU opposite Acoding strandcoding strandcoding strandRNAtemplate strandRNA5′3′3′5′5′3′3′5′5′3′
  1. A gene: two strands of DNA, held by hydrogen bonds.
  2. RNA polymerase parts the strands.
  3. RNA nucleotides pair with the template strand: U opposite A.
  4. The enzyme joins them into a strand and moves on; the DNA closes behind it.
  5. The RNA has the coding strand's sequence, with U in place of T.

D1.2.3 D1.2.4 Stable templates, gene expression

Read for a lifetime, read when needed

Transcription reads the template; it does not use it up. The hydrogen bonds open for a moment and close again, the covalent backbone is never broken, and no base is changed. So one gene can be transcribed again and again, and every copy of its mRNA matches.

That matters most in somatic cells that never divide again. Most of the nerve cells in the outer layer of your brain are as old as you are, and heart muscle cells are replaced only very slowly, so the genes in each have to be read for decades. Their base sequences must be conserved: held without change for the whole life of the cell. DNA suits the job, with two strands, a strong backbone and a home in the nucleus. (Cells also repair damage to DNA; that is D1.3.)

Every somatic cell of one person has the same genome, yet no cell uses all of its genes. A gene is expressed when its information is used to make its product. That is gene expression, and it has two main steps: transcription copies the gene into mRNA, and translation (chapter 3) uses the mRNA to build a polypeptide. A gene that is being transcribed is switched on, and one that is not is switched off. The more often it is transcribed, the more mRNA, and the more of its protein, the cell makes. Some genes are switched on and off as conditions change. Which genes a cell transcribes is what makes it a particular kind of cell: a pancreatic beta cell transcribes the insulin gene and a skin cell does not, so each is specialised for its own job.

  • Transcription reads a template without changing it, so one gene gives many identical mRNAs.
  • Not all genes are expressed in a cell at one time, and transcription is where a gene is switched on or off.

How a gene is switched on at its promoter is chapter 9.

Watch out Different cells do not have different genes. They have the same genes and transcribe different ones.

A nerve cell in your brain is 60 years old and has never divided. Its genes have been transcribed all that time. What has happened to their base sequences?

pancreatic beta cellits mRNAnot transcribednot transcribeddeveloping red blood cellnot transcribedits mRNAnot transcribedskin cellnot transcribednot transcribedits mRNAinsulin genebeta-globin genekeratin genethe same stretch of chromosome in all three cells
The same three genes sit in every one of these cells. Which one is being copied changes from cell to cell.
Watch RNA polymerase copy one strand of a gene. Then switch the gene off.

D1.2.5 D1.2.6 Translation

Three kinds of RNA build a protein

Translation makes a polypeptide whose order of amino acids is set by the base sequence of an mRNA. It happens at ribosomes, some free in the cytoplasm and some on the rough endoplasmic reticulum.

A ribosome is made of ribosomal RNA (rRNA) and protein, in two parts. The mRNA binds to the small subunit. The large subunit can hold two tRNAs at once, side by side, and it joins their amino acids (the rRNA is what speeds up that joining).

Transfer RNA (tRNA) molecules are short, single strands of RNA that fold back on themselves into a compact shape. Each carries one particular amino acid at one end, and has three exposed bases at the other, its anticodon, which chapter 4 is about. There are many kinds of tRNA, at least one for every amino acid.

So the three kinds of RNA share the work. The mRNA, a long single strand whose bases are read in threes, carries the message, the rRNA in the ribosome holds it and joins the amino acids, and the tRNAs bring the amino acids in. What holds the message in place, base to base, is hydrogen bonds again.

  • mRNA binds to the small subunit of the ribosome.
  • Two tRNAs can bind at the same time, in the large subunit.
Watch out Ribosomes do not make amino acids. They join the amino acids that tRNAs bring.

The large subunit holds two tRNAs at the same moment. Why two, and not one?

AUGGCUAAGUGGrRNACGAUUCAlaLysMetlarge subunitsmall subunittRNAmRNApolypeptide5′3′EPA

Tap a part of the ribosome.

A ribosome part way along an mRNA: two tRNAs are in place, a short chain hangs from one of them, and the next codon waits.

D1.2.7 Codons and anticodons

Codon meets anticodon

The mRNA is read three bases at a time. Each group of three is a codon. A tRNA carries a matching group of three exposed bases at one end, its anticodon, and one particular amino acid at the other end.

In the ribosome an anticodon pairs with a codon by complementary base pairing, held by hydrogen bonds: A with U and C with G. A tRNA whose anticodon fits stays long enough for its amino acid to be joined to the chain, and any other tRNA drifts away again. So the right amino acid arrives because the right tRNA pairs, and each kind of tRNA always carries the same amino acid, which is what keeps the code accurate.

Anticodons contain U, never T, because a tRNA is RNA. There is a neat consequence: an anticodon has the same bases as the template strand's triplet for that codon, with U where DNA has T. Take the codon GCU: its anticodon is CGA, on a tRNA that carries alanine. At higher level you also write the ends: the codon is 5′-GCU-3′ and the anticodon 3′-CGA-5′.

  • A codon sits on mRNA, an anticodon on tRNA.
  • Pairing is complementary, A with U and C with G, so a codon decides which tRNA fits.
Watch out Codons are on mRNA and anticodons are on tRNA. DNA has neither: its triplets are just triplets.

A codon reads U G G. Which anticodon pairs with it?

Tap a tRNA to dock it on the open codon (or drag it up). Which one pairs with GCU? Read all three bases.

Each base's pairing edge has knobs and notches: a knob fits a notch, a flat edge fits a flat edge. The same rule decides which tRNA fits each codon. (A real ribosome holds two tRNAs at a time and moves on; here each codon keeps its tRNA so you can compare them.)

D1.2.8 D1.2.9 The genetic code

A code written in threes

The genetic code says which amino acid each codon stands for. A cell uses four bases and twenty amino acids. One base for each amino acid gives only 4 meanings, and two bases give 4 × 4 = 16, still too few. Three bases give 4 × 4 × 4 = 64, more than enough. So the code is a triplet code.

Of the 64 codons, 61 code for amino acids. The other three, UAA, UAG and UGA, are stop codons: they code for nothing and end the chain. AUG codes for methionine and is also the start codon, where translation begins. With 61 codons for 20 amino acids, most amino acids have more than one codon, so the code is degenerate: leucine, serine and arginine have six each, methionine and tryptophan only one. Degenerate never means ambiguous, because no codon stands for two amino acids.

The code is also universal: almost every living thing reads each codon as the same amino acid, from bacteria to people. A few small exceptions exist (the mitochondria of vertebrates, ours included, read UGA as tryptophan), but they are rare. A code this arbitrary, shared by all life, points to one common ancestor (A1.2.10). It is also why bacteria given the human insulin gene make human insulin, which is how insulin for people with diabetes is made.

Why can the code not use pairs of bases for each amino acid?

20 amino acidsstopeach small block is one base:ACGU

1

1 base: 4 codons for 20 amino acids. Sixteen amino acids are left with no codon at all.

Each column is one amino acid (the shapes on top), and the blocks stacked under it are the codons that stand for it. At three bases, the last column holds the stop codons.
second base1st3rdUCAGUUUUU PheUCU SerUAU TyrUGU CysCUUC PheUCC SerUAC TyrUGC CysAUUA LeuUCA SerUAA StopUGA StopGUUG LeuUCG SerUAG StopUGG TrpCUCUU LeuCCU ProCAU HisCGU ArgCCUC LeuCCC ProCAC HisCGC ArgACUA LeuCCA ProCAA GlnCGA ArgGCUG LeuCCG ProCAG GlnCGG ArgAUAUU IleACU ThrAAU AsnAGU SerCAUC IleACC ThrAAC AsnAGC SerAAUA IleACA ThrAAA LysAGA ArgGAUG MetstartACG ThrAAG LysAGG ArgGUGUU ValGCU AlaGAU AspGGU GlyCGUC ValGCC AlaGAC AspGGC GlyAGUA ValGCA AlaGAA GluGGA GlyGGUG ValGCG AlaGAG GluGGG GlyUCAGUCAGUCAGUCAGUCAGUCAGUCAGUCAGUCAGUCAGUCAGUCAGUCAGUCAGUCAGUCAGUCAGUCAGUCAGUCAGUCAGPheLeuSerTyrStopCysStopTrpLeuProHisGlnArgIleMetThrAsnLysSerArgValAlaAspGluGlystart codonstop codon
  1. The genetic code: 64 codons, read from the first base to the third.
  2. Find the first base, then the second, then the third: GCU is alanine.
  3. The wheel holds the same code, read from the centre out.
Tap three bases, or an amino acid. Paste a strand to translate it, or start a round of ten under it to practise reading the code.

In an exam you are given the table of mRNA codons: you learn how to use it, not what is in it. Read the mRNA in threes from the start codon. The first base picks the row, the second the column, and the third the line in the box. Stop at a stop codon. A coding strand reads as the mRNA with T swapped for U, but a template strand has to be paired first. Where you start sets the reading frame: start one base along and every codon changes.

How we know it is threes In 1961 Francis Crick, Sydney Brenner and their colleagues added bases to a gene of a virus that infects bacteria. One extra base wrecked the gene, and so did two, but three put it right again. If the code is read in threes, three extra bases add one codon and leave the rest in step. (This goes beyond the syllabus, and D1.3 comes back to bases added and lost.)
Watch out Degenerate means several codons for one amino acid, never one codon for several. And universal means every organism reads the code the same way, not that every organism has the same genes.

Use the table: what does the mRNA 5′-AUG AAA CCG UGG UAG-3′ code for?

D1.2.10 Elongation

One codon at a time

Once translation has started, the polypeptide grows by a cycle that repeats for every codon. This is elongation, and it is the part of translation this chapter follows. How translation starts is chapter 11.

  • A tRNA whose anticodon pairs with the codon in the free place binds, bringing its amino acid.
  • The ribosome joins the chain to that amino acid with a peptide bond. This is a condensation reaction, so a molecule of water is released, and the chain now hangs from the newest tRNA.
  • The ribosome moves one codon, three bases, along the mRNA, towards its 3′ end.
  • The tRNA that handed over the chain leaves, free to collect another amino acid.

The chain grows by one amino acid for every codon, in the order of the codons. A human ribosome adds about five amino acids a second, so a protein of 300 amino acids takes about a minute. At a stop codon no tRNA pairs, and the polypeptide is released.

Two kinds of bond do two jobs here. Hydrogen bonds hold codon and anticodon together for a moment. Peptide bonds, which are covalent, hold the chain together for good.

Watch out Amino acids in the chain are joined by peptide bonds, not hydrogen bonds. The hydrogen bonds are between codon and anticodon, and they break as each tRNA leaves.

A polypeptide is 150 amino acids long. How many codons did the ribosome read to make it, counting the codon that ended it?

large subunitsmall subunitAUGGCUAAGUGG5′3′UACMetCGAAlaMetpeptide bondHHOLysUUCnext tRNAempty tRNArepeattowards the 3′ end
  1. The next tRNA pairs with the open codon.
  2. A peptide bond joins the chain to its amino acid.
  3. The ribosome moves one codon along.
  4. The empty tRNA leaves. Repeat.
Watch each tRNA find its codon and the chain grow. Then change one base of the mRNA and run it again.

D1.2.11 Mutations that change protein structure

One base, one amino acid

A mutation is a change in the base sequence of a gene. A point mutation changes one base, and the commonest kind is a base substitution: one base swapped for another, which changes one codon. What that does to the polypeptide depends on the new codon. If it stands for the same amino acid, the mutation is silent, which the code's degeneracy allows. If it stands for a different amino acid, it is missense. If it is a stop codon, it is nonsense, and the chain ends early, usually too short to work. (Bases added or lost, and what causes mutations, are D1.3.)

Sickle cell anaemia is the guide's example of a point mutation that changes a protein. Haemoglobin carries oxygen in red blood cells. In the gene for its beta chain, codon 6 on the coding strand changes from GAG to GTG (on the template strand, CTC becomes CAC), so the mRNA codon changes from GAG to GUG and glutamic acid (Glu) becomes valine (Val). (The positions are counted from the first amino acid of the finished chain, which is valine, because the starting methionine is removed. Counted from the start codon this is the seventh codon.)

One amino acid matters because of where it sits. Glu is charged and hydrophilic, and Val is non-polar. Position 6 lies on the outside of the haemoglobin molecule, so the valine makes a non-polar patch there that sticks to a pocket on a neighbouring molecule. When oxygen is low, the molecules join into long stiff fibres that bend red blood cells into sickle shapes. The sickled cells block small blood vessels, which causes pain and damage to organs, and they are destroyed early, so the person has too few red blood cells, which is sickle cell anaemia. The haemoglobin itself still carries oxygen: the harm comes from the fibres, and from the cells' shape and short life.

Remember it What a substitution can do

  • SameSilentthe same amino acid
  • SwappedMissensea different amino acid
  • StoppedNonsensea stop codon: the chain ends early
Watch out A mutation changes the gene, not the protein directly: the changed protein follows from the changed codon. And not every substitution changes the protein.

In a gene, one base changes so that an mRNA codon GAA becomes GAG. What happens to the polypeptide?

normalsickle cellcoding strand, numbered by position in the finished chainmRNAamino acidshaemoglobin molecules when oxygen is lowred blood cells in a small blood vesselACT4CCT5GAG6GAG7ACUCCUGAGGAGThrProGluGluACT4CCT5GTG6GAG7ACUCCUGUGGAGThrProValGlua fibreapartblocked
  1. One base differs in the gene for haemoglobin's beta chain.
  2. So one codon in the mRNA differs.
  3. So one amino acid differs: valine for glutamic acid.
  4. The non-polar valine makes the molecules stick into fibres.
  5. Fibres bend the cells into sickles that block small vessels.

Six one-base changes to the demonstration gene's mRNA (GCA AUG GCU AAG UGG GGC UAA, where codon 1 is AUG). Use the table in chapter 5, then drop each into the bin it belongs in.

0 of 6 sorted

Pick a change (tap it, or Tab to it and press Enter), then pick the bin it belongs in.

Each change swaps one base in one codon. What does the new codon stand for?
ribosomeMVH+LTPE−E−K+SAVTAMVH+LTPE−E−K+SAVTALWGK+VNVD−E−non-polarpolarpolar, with a chargecysteine (C)15 weak bonds holdits shapeS-S0 strong bondsbetween two cysteinesA gene, readcodon by codon23 amino acidsleave the ribosomeone at a time
  1. The gene is transcribed and translated: Its 23 amino acids are joined by 22 peptide bonds: one of 2023 (about 8 × 1029) possible chains this long. A ribosome makes the chain one amino acid at a time, and it starts to fold as it comes out.
  2. It folds into a shape of its own, held by weak bonds between its side chains.
Fold the start of the beta-globin gene, make the sickle cell change, fold both and make a second copy of each.
AAACCGGGTTUUOrder 1: a short peptideIt starts with Met (methionine).RNA polymerasestart of the geneTap the strand to copy.Order 1: a short peptideRNA polymeraseACGTUthe trayOrder 1: a short peptideCCGMetGlySerPheLeuTyrthe rackClinic sampleTwo alleles of one genestart12345678normalsickle cellnormal, amino acid 6?sickle cell, amino acid 6?
  1. Which strand will you copy?
  2. Pick the base that pairs: RNA has U, not T.
  3. Which tRNA’s anticodon pairs with this codon?
  4. One base differs. What does it do to the protein?

D1.2.12 Directionality

Five prime to three prime, both times

From A1.2 you know that the carbons of a nucleotide's sugar are numbered 1′ to 5′. A strand has a 5′ end, where the last nucleotide has a phosphate on its carbon 5′, and a 3′ end, where the last nucleotide has a free OH on its carbon 3′. So every strand has a direction.

5′ to 3′ transcription means that RNA polymerase joins the 5′ phosphate of each incoming RNA nucleotide to the 3′ OH at the end of the growing RNA (the sugar is ribose, because this is RNA). The new link is a covalent bond, the same sugar-phosphate bond that forms the backbone of a strand (A1.2). A nucleotide can only be added at the 3′ end, so the RNA is built from its 5′ end to its 3′ end. The template runs the opposite way to the RNA, so the polymerase reads the template 3′ to 5′. The coding strand runs the same way as the RNA, which is why its sequence, written 5′ to 3′, matches the mRNA's.

Translation runs 5′ to 3′ too. The ribosome starts near the mRNA's 5′ end and moves towards its 3′ end, so the codons are read in that order, and the first amino acid of the polypeptide comes from the codon nearest the 5′ end. Direction matters: read the other way, the same bases make different codons and a different polypeptide, and the start codon is found only by moving 5′ to 3′ from the 5′ end (chapter 11). By convention a sequence is written 5′ to 3′, left to right, unless it is labelled otherwise.

Watch out 5′ and 3′ name carbons of the sugar. The polymerase moves along the template from its 3′ end towards its 5′ end, while the RNA it makes grows 5′ to 3′: two directions, one movement.

A template strand reads 3′-TACAAGCGT-5′. Written 5′ to 3′, what is the mRNA?

RNApolymeraseTHGHCHAHCHGHAOHCOHGOHUOHGOHGOHGOHGCAAUGGCUAAGUGG5′3′first codon readthe ribosome moves 5′ → 3′joins hereno free 3′ OHherereads thetemplate3′ → 5′template strandRNA3′5′5′3′3′
  1. The polymerase reads the template 3′ to 5′.
  2. Each new nucleotide joins the RNA's 3′ end.
  3. Nothing can join at the 5′ end.
  4. The ribosome reads the mRNA 5′ to 3′ too.

D1.2.13 D1.2.14 Promoters and non-coding DNA

Where a gene starts, and DNA that codes for nothing

The promoter is a stretch of DNA just before the part of a gene that is transcribed. It is not transcribed itself. It is where transcription starts. Transcription factors are proteins that attach to the promoter, and RNA polymerase can bind and start only when the right ones are in place (you do not have to name any). Which factors a cell makes decides which of its genes are transcribed: that is the switch from chapter 2. Some factors promote transcription and others block it. The promoter is a whole region, not one named sequence.

Non-coding sequences are stretches of DNA that code for no polypeptide. In humans only about 1 to 2% of the genome codes for polypeptides, and the rest includes:

  • regulators of gene expression: promoters, and other sequences where factors bind;
  • introns: stretches inside a gene that are transcribed but cut out of the RNA (chapter 10);
  • telomeres: repeats of a short sequence (TTAGGG in humans) at each end of a chromosome, which protect the genes near the ends when the DNA is copied;
  • genes for rRNA and tRNA: they are transcribed, and the RNA is the product. It is never translated.

Non-coding does not mean useless. Every one of these has a job, and none of them codes for a polypeptide.

Watch out Non-coding is not the same as not transcribed. Introns and the genes for rRNA and tRNA are transcribed, while the promoter is not, and is never part of the mRNA. Telomeres code for no polypeptide.

A gene for a tRNA is transcribed in every cell, but its RNA is never translated. Is it coding or non-coding DNA?

RNA polymeraseno transcription factors:cannot bindRNA polymeraseRNA beginstranscription factors are boundpromoter (not transcribed)gene (transcribed)direction of transcription
The promoter (pale pink band) is DNA just before the gene. Its bumps are where transcription factors fit.
123telomeretRNA generegulatorysequencepromotera gene that codes for a polypeptiderRNA genetelomerecodes for a polypeptidedoes not

Tap a part of the chromosome.

One stretch of chromosome, drawn to show kinds of DNA, not to scale. Only the exons code for the polypeptide.

D1.2.15 D1.2.16 RNA processing and alternative splicing

Capped, cut and tailed

In a eukaryotic cell, the RNA that RNA polymerase makes from a protein-coding gene is pre-mRNA. It is changed in the nucleus before it leaves, a stage called post-transcriptional modification, and the result is mature mRNA.

In splicing, the introns are cut out and the exons joined end to end, so the mature mRNA carries only sequence that codes for the polypeptide. The cut-out introns are broken down in the nucleus. The two ends are protected as well. A 5′ cap, a modified guanine nucleotide, is added to the 5′ end, and a poly-A tail, a long run of adenine nucleotides (often about 200), to the 3′ end.

The reason is that enzymes in the cytoplasm break RNA down from its ends. The cap and the tail protect, and so stabilise, the mRNA, which then lasts long enough to be translated many times. The cap also helps the ribosome find the mRNA's 5′ end (chapter 11). Prokaryotes do not cap, tail or splice their mRNA in this way (most of their genes have no introns), and with no nucleus, translation can start before transcription has ended.

Alternative splicing: in many genes, which exons are kept can vary. Leave an exon out, or keep a different one, and the mature mRNA codes for a different polypeptide. So one gene can code for several polypeptides, and a cell's set of proteins is much larger than its number of genes: about 20,000 human protein-coding genes make many more proteins than that. You need no named example, and the gene in figure 10.2 is invented.

Remember it Introns and exons

  • InIntronscut out and broken down in the nucleus
  • ExitExonsjoined, and leave in the mature mRNA
Watch out Introns are cut out of the RNA, not out of the gene: the DNA keeps them. And alternative splicing changes which exons are kept, not the gene's sequence.

A gene has four exons. Exons 1 and 4 are always kept, and exons 2 and 3 can each be kept or left out. How many different mature mRNAs can it make?

nucleuscytoplasmnuclear pore5′ cap1234AAAAAApoly-A tail5′3′3′3′pre-mRNAmature mRNAintrons stay in the nucleusexonintron
  1. Pre-mRNA: exons and introns.
  2. A 5′ cap is added.
  3. A poly-A tail is added.
  4. Introns are cut out and the exons spliced together.
  5. Mature mRNA leaves the nucleus.
one gene,as pre-mRNA1234mature mRNA12341234polypeptide version 1134exon 2 is left out134polypeptide version 2
An invented gene. Each exon codes for four amino acids, and the colours follow each exon into the polypeptide.
Start at the promoter, then cap, tail and splice the RNA. Try the other splice, or take the transcription factor away.

D1.2.17 Initiation of translation

Starting the chain

Initiation is how translation starts. It happens in this order:

  • the small subunit attaches to the mRNA at its 5′ terminal, its 5′ end (in eukaryotes the 5′ cap helps);
  • it moves along the mRNA, 5′ to 3′, to the first AUG, the start codon (the short stretch before it is not translated);
  • the initiator tRNA, anticodon UAC, carrying methionine, pairs with AUG;
  • the large subunit joins, so the ribosome is complete, with the initiator tRNA in the P site;
  • another tRNA, matching the next codon, binds in the A site.

The large subunit has three places for tRNAs, and they are used all through elongation. The A site is where each new tRNA arrives with its amino acid. The P site holds the tRNA carrying the growing chain, which is joined by a peptide bond to the amino acid in the A site. The E site is where an empty tRNA goes when the ribosome moves one codon, and where it leaves from. After each move the tRNA that carried the chain is in the P site, and the A site is free over the next codon.

Every new polypeptide begins with methionine, because the start codon codes for it, but in many proteins that methionine is removed afterwards. Haemoglobin's beta chain, for example, begins with valine in the finished protein, which is why chapter 7 counted from there.

Remember it The three sites

  • ArriveA sitea loaded tRNA arrives
  • PassP siteholds the chain and passes it on
  • ExitE sitethe empty tRNA leaves
Watch out The initiator tRNA starts in the P site, not the A site. Every other tRNA enters at the A site and reaches the P site only when the ribosome moves. And the small subunit binds the mRNA first, the large subunit after it.

The first peptide bond has just formed, joining methionine to the second amino acid. Before the ribosome moves, which site holds the tRNA carrying both amino acids?

GCAAUGGCUAAGUG5′cap3′small subunitEPAEPAUACMetinitiator tRNAstart codonCGAAlaMet
  1. The small subunit attaches at the mRNA's 5′ end.
  2. It moves to the start codon, AUG, where the initiator tRNA pairs.
  3. The large subunit joins: the initiator tRNA is in the P site.
  4. The next tRNA arrives in the A site.
  5. A peptide bond joins the two amino acids.
  6. The ribosome moves one codon; the empty tRNA leaves from the E site.
Watch translation start at the 5′ end, then follow each tRNA through the A, P and E sites.

D1.2.18 D1.2.19 Modification and proteasomes

Finished, then recycled

Many polypeptides cannot work as they come off the ribosome. They are modified first, which is called post-translational modification: they are cut, folded and bonded, or given extra groups such as sugars or phosphates. Insulin is the guide's example, and it is made in two stages.

It starts as pre-proinsulin, 110 amino acids long, which begins with a signal peptide of 24 amino acids. The signal peptide sends the ribosome to the rough ER, so the chain is threaded into the ER as it is made. In stage 1, in the rough ER, the signal peptide is cut off, leaving proinsulin (86 amino acids). Proinsulin folds, and three disulfide bonds form: two join what will become the B chain to the A chain, and one lies within the A chain. In stage 2, in the Golgi apparatus and the vesicles that bud from it, enzymes cut out the middle section, the C-peptide, leaving insulin: an A chain of 21 amino acids and a B chain of 30, held together by two disulfide bonds. Insulin is stored in vesicles until it is released (what it does is D3.3).

Insulin's two chains are 21 and 30 amino acids long, and pre-proinsulin is 110. How many amino acids are cut away in all?

Cells break proteins down as well. A proteasome is a barrel-shaped complex of proteins, in the cytoplasm and the nucleus, that hydrolyses the peptide bonds of a protein into short pieces, which other enzymes then split into single amino acids for the cell to use again in building new proteins. A protein is marked for breakdown with a small protein tag. Damaged and misfolded proteins carry one, and so do healthy proteins the cell no longer needs. A protein's life may be minutes or months.

The proteome is all the proteins a cell makes. Keeping it working needs constant breakdown and synthesis: broken proteins are cleared away, and the amount of each protein can change quickly when the cell needs something new. The protein factory after chapter 7 has orders for this chapter too, when the page is at higher level.

Watch out A polypeptide straight off the ribosome is not always a working protein. And proteasomes do not only destroy faulty proteins: they also clear healthy ones the cell no longer needs.

A cell makes a protein and breaks it down again within an hour. Is that wasteful?

rough ER membraneinside the ERribosomesignal peptideproinsulinsignal peptidecut offS–SS–SS–Sproinsulin, foldeddisulfide bondsS–SS–SS–Svesicle from the GolgiC-peptide cut out at both endsinsulin: two chains held by disulfide bondsBAC-peptide
  1. Pre-proinsulin: a signal peptide sends it into the rough ER.
  2. Stage 1: the signal peptide is cut off, leaving proinsulin.
  3. Proinsulin folds and disulfide bonds form.
  4. Stage 2: the C-peptide is cut out.
  5. Insulin: two chains held by disulfide bonds.
proteasomea small tag marks ita misfolded proteinHHOHHOwater splits eachpeptide bond(hydrolysis)free amino acidsa ribosome buildsa new chain
  1. A tagged protein reaches a proteasome.
  2. Its peptide bonds are hydrolysed.
  3. The amino acids are used again to build new proteins.

02Check

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03Downloads

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04Teacher resources

The guide as three one-hour lessons, and three more at higher level. Each has a plan to print (the timings, what to project and where to stop, the activities with what they need, what students get wrong) and slides to teach it from, in the same order, with the teacher's moves in the notes.

LessonCoversFocusChaptersLesson planSlides
1Copying a gene D1.2.1 to D1.2.460 min Transcription by RNA polymerase, complementary pairing, a template that never changes and genes switched on or off 1, 2 Lesson planPDF 682 KB SlidesPPTX 4.4 MB
2Codons and the code D1.2.5 to D1.2.960 min mRNA, ribosomes and tRNA; codons and anticodons; why the code is in threes; reading the table 3, 4, 5 Lesson planPDF 662 KB SlidesPPTX 667 KB
3Building the chain, and one base wrong D1.2.10, D1.2.1160 min Elongation one codon at a time, peptide bonds, and how one substitution causes sickle cell anaemia 6, 7 Lesson planPDF 697 KB SlidesPPTX 2.8 MB
4Direction, promoters and non-coding DNA HL D1.2.12 to D1.2.1460 min The direction of transcription and translation, transcription factors at the promoter, and DNA that codes for no polypeptide 8, 9 Lesson planPDF 678 KB SlidesPPTX 589 KB
5Processing and starting translation HL D1.2.15 to D1.2.1760 min Caps, tails and splicing, one gene giving several polypeptides, and how translation starts 10, 11 Lesson planPDF 682 KB SlidesPPTX 6.2 MB
6Finishing, recycling, and the whole factory HL D1.2.18, D1.2.1960 min Pre-proinsulin to insulin, proteasomes and a working proteome, then the whole process in the protein factory 12 Lesson planPDF 617 KB SlidesPPTX 530 KB
PDFEvery lesson planAll six plans in one PDF, with this overview at the front. 1.4 MB KEYNote template, filled inThe class’s note template with every gap filled. 2.0 MB

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How this was made. The course structure, the activities and the teaching choices come from my own classroom, my presentations and my years of teaching IB and AP Biology. I use Claude, an AI, to help write and build the interactive guides, lesson plans, slides and practice questions, and to draw the diagrams and code the interactives. I direct the work and review it against the IB and AP specifications before it goes live.