What are Plasmids?

Aug 24th, 2007

Today sees the European release of the game Bioshock, an FPS which has been receiving plaudits and review scores which are truly astounding, with Metacritic reporting aggregate review scores of 96/97% for the PC and XBOX360 versions respectively. I don’t normally play FPSs, but I’m sorely tempted by what is clearly an astounding game.

*Warning* The rest of the post contains very minor spoilers. If you already know how the title of the post relates to the game then this will reveal nothing new and you can safely read on. If you have avoided as much coverage as possible, and have avoided all media coverage, then you may wish to stop reading, or at least skip the next paragraph. *Warning*

As part of the game you are able to modify yourself with various power-up called plasmids, remains of the genetic engineering that occurred in the society you are exploring. (That’s it. That’s the end of the spoilers, I told you they were minor.) But what are plasmids? Are they just an invention of the games designers?

Well obviously plasmids don’t exist in the same way they do in the real world, but the idea comes from a very real concept, and a tool which is vitally important in modern molecular biology. (Okay, so I fooled you, its a science post, not a gaming post. But you’re reading now, and can’t you at least pretend to be interested.)

Plasmids are small circles of DNA, the molecule which forms your genetic code. Like the DNA found within the nucleus of every nucleated cell in your body* the DNA of plasmids form a double helix structure, a twisted ladder like structure in which the phosphate backbone forms the side of the ladder and the so called ‘bases’ form the rungs. Four different nucleotides form the bases, Adenine, Guanine, Thiamine and Cytosine or A, G, T and C for convenience. Two bases form each rung and these are paired predictably A with T and C with G. It is these letters which form the genetic code, and a string of letters form a gene. Whereas your genome consists of approximately 3 giga bases (3,000,000,000 pairs of nucleotides) a plasmid is much smaller, typically being a few thousand base pairs long in size.

In the wild plasmids are found in bacteria, their short sequence contains regions that allow them to be maintained and replicated, as well as genes encoding for certain traits. The small size of the plasmid allows it to be shuffled between nearby cells quickly, allowing it to spread through the population. Some plasmids have features that further help facilitate this, such as through encoding injection needles whereas others make toxins to kill of surrounding bacteria, or even the host bacterium itself should it loose the plasmid. The plasmids allow the bacteria to rapidly adapt to changing environments, and often contain genes such as antibiotic resistance can then rapidly spread.

Plasmids are ideal for lab use, as their small size makes them easy to manipulate. This allows individual genes to be inserted into plasmids and then be modified, such as by introducing mutations or adding tags. We can then shift them easily in and out of bacteria, and in some cases make the bacterium express the gene we want, changing its characteristics. It is this technique that allows us to artificially produce insulin for diabetics, reducing our reliance on animal products. Often these will be introduced alongside markers, such as resistance to antibiotics (the bacteria used are non pathogenic, and are killed before they are disposed of) or production of pigmented products.

So indeed plasmids can be used to introduce new ‘powers’ into bacteria, but what of other organisms?

Well I work on yeast, which is another single celled organism, and can also be transformed (changed) with plasmids containing the appropriate sequences. This is extraordinarily useful when you actually work with yeast, as it is really easy to introduce mutated genes.

But with multi-cellular organisms plasmids aren’t quite so great, and can generally only be maintained for a short period of time as they are lost easily when cells divide. However it is still possible to introduce plasmids into plant and animal tissues, and induce gene expression, although actually getting the Plasmid DNA in there is difficult. With plants it is possible to use a deliciously crude method known as biolistics, where the DNA is literally fired into the cells on tiny gold particles. With animals, liposomes (tiny lipid — fat — bubbles containing DNA) are able to introduce material into cells, but must be applied directly ie. in the form of an aerosol, and are ultimately pretty ineffective.

However other approaches, such as the use of modified viruses, may prove more successfully for long term modification of mammalian tissues. Generally those which involve the integration of the new DNA into the cells normal DNA. (This is a process know as gene therapy. Early trials have been mixed, suffering from problems of immune reaction, cancer caused by bad integration sites, and generally poor results.)

Long term, safe, introduction of new genes into human tissues is still a long way off. However when/if it does come about it is possible that plasmids of some form will indeed be central to the process. However, and perhaps unsurprisingly, the resultant changes are likely to be small and localised corrections of genetic diseases. Moreover it is unlikely changes will be immediate, or easily reversible, at least not for the foreseeable future.

* Cell containing a nucleus. Red blood cells, technically corpuscles, for example don’t contain a nucleus and therefore don’t contain (most of **) your DNA.

** One of my problems is that I can’t honestly simplify things down to the point of being wrong. It makes me feel dirty. But I shan’t go into detail here as otherwise I’ll end up writing a biology textbook as I clarify all these points.


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