Making human insulin by GM sim
Cut the human insulin gene and a plasmid with the same restriction enzyme, see the sticky ends pair base by base, seal them with DNA ligase, put the plasmid into bacteria, select them on antibiotic agar and grow them, one step at a time and in order.
Genetic modification: making human insulin · covers the O-Level, IGCSE, GCSE topic
What the sim shows
How human insulin is made by genetic modification, step by step. Cut: the same restriction enzyme (enzyme A) cuts the human DNA either side of the insulin gene, and opens the plasmid. It cuts each strand at its recognition site (GAATTC), one base in from the end of the site, so the cut is staggered and leaves short single-stranded sticky ends: AATT on one strand, facing TTAA on the other (that strand read 3′→5′; read 5′→3′, both sticky ends are AATT). A different enzyme (enzyme B, site GGATCC) leaves GATC ends, which cannot pair with AATT. Join: the gene's sticky ends pair with the plasmid's by complementary base pairing (A with T, C with G), held by weak hydrogen bonds; DNA ligase then seals the sugar-phosphate backbone. The result is a recombinant plasmid, the vector. Insert: the plasmids are mixed with bacteria, and only some bacteria take one up. Select: the plasmid carries a gene for resistance to an antibiotic (a marker gene), so on agar with that antibiotic only bacteria that took up a plasmid grow. This shows that a bacterium took up a plasmid, not that the plasmid has the insulin gene: a cut plasmid can also close up on itself without the gene, so further checks are needed to pick out a colony with the gene (the model assumes the colony grown has passed them). Grow: the chosen bacteria divide, about every 20 min in good conditions (illustrative), copying the plasmid each time, and express the gene to make human insulin. They are then grown in large numbers in a fermenter, and the insulin is extracted and purified. Simplified on purpose: sizes are not to scale (the cell model is about 3 400 times life size for a 20 µm cell, the bacterium about 62 000 times for a 2 µm one, so a real bacterium is about ten times smaller than the cell, not larger as on the bench). Each bead stands for a stretch of DNA, not one base; a real plasmid has thousands of base pairs, and the real gene is far longer than shown. The bases beside each site are made up for the model, enzymes A and B are modelled on EcoRI and BamHI, and in this model enzyme B's site lies inside the gene. Only some bacteria take up a plasmid: 3 of 12 here, far fewer in real life. In real production the gene is usually made as copy DNA from the insulin mRNA, because bacteria cannot remove the non-coding sections (introns) of a human gene. Human insulin is two short chains, A and B: these were first made separately by bacteria and then joined; later methods make a single chain, proinsulin, which is then processed into insulin. This model shows one gene and one product. The gene can also go into the plasmid the wrong way round, which the further checks also look for; this is not modelled. The heat shock or calcium treatment used to help bacteria take up plasmids is left out.
- Coloured beads: the insulin gene (human DNA) and the resistance gene (plasmid)
- Lids: blue, enzyme A · orange, enzyme B · green, DNA ligase
- Striped plate: agar with the antibiotic · plain plate: agar only
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