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July 7, 2000

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Celera

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Subject:  Re: gene expression?
Author:  davefeatherstone

[Kevin asked:] What exactly is gene expression? ...and how can you measure or quantify the level of a gene's expression?

I'm sure its similar, but I'll ask the same question for protein expression and the level or the quanification of that.


DNA is nothing but a big stringy chemical. It does, basically, nothing. However, in every cell in every organism, there are little 'machines' made of protein and RNA (another chemical a lot like DNA) that make almost-identical copies of little parts of the DNA. These copies happen to be made of RNA. Sort of like a bunch of monks each transcribing little parts of the bible. The bible does nothing but sit there, and these monks crank out copies. Sometimes the monks make mistakes; quite often they consitently skip parts, etc. They're pretty choosy, and we don't really know why except we know what sorts of things they like to copy and can now predict them with imperfect software ('genefinder software'). Anyway, for those who haven't gotten the analogy yet: DNA is the bible, the little copies are RNA. Generally, this RNA is then 'edited' and the resulting edited RNA is 'translated' into proteins, which are other chemicals that get all crumpled up and amazingly do essentially all the work of building and maintaining life.

The little parts the monks choose to copy are called 'genes'. Genes thus encode proteins.

In some cells and tissues, the monks are hard-working sorts who write out genes like mad. In other cells, the monks are all lazy bastards who hardly do a thing. In different cells, the monks have different parts of the DNA bible they like to copy. Thus, a certain gene could get 'transcribed' like crazy in one place and not at all in another. 'Gene expression' in the first place would be high, and low in the other. And biologists quantify gene expression the same way you'd do it for the monks: you basically count the number of copies (RNAs) produced for each part(gene) of the bible (DNA).

For protein expression, it's basically the same. You count the number of proteins produced. Some RNAs are pretty durable, so you have time to make a lot of proteins from them before they degrade. Other RNAs are wispy crappy little things on tissue paper that you can't hardly use but once. Similarly, some proteins are durable, others are cheap things that break after a few uses. Thus, if you make quality proteins, they'll hang out longer and you'll have more. Thus that protein's 'expression' will be higher even though maybe not as many are made. So two things go into expression: the number of copies and how long they last. Just like cars. If you want to know the number of Toyotas likely to be on the road, you see how many are being made each year and how long they last.

So, anyway, the flow goes like this:

DNA --> RNA --> Protein

This is so important it's called 'central dogma' in biology or something like that (I don't really remember the term for sure; it's one of those useless phrases intro biology makes one memorize, but then you forget). Anyway, it's important.

Every cell (you have trillions) has a couple copies of DNA, but they sort of do weird things to each other so it's more like one unique copy. Some organisms (plants) have a bunch of copies, but they're weird. Who cares. The point is that from that DNA is made zillions of RNAs, each representing a little bit of DNA. Generally, each little RNA represents one gene, but that's not always true. Then each RNA is used to make protein. Basically, the number of RNAs for any gene is that gene's 'expression'. The number of proteins for any gene also that gene's expression, but it's not really called that, since genetics people are weird and like to pretend nothing happens outside the nucleus (the part of the cell where the DNA is) or something. Anyway, protein amount is protein expression.

So in terms of expression, it's like this:

DNA (a bit) --> RNA (lots more) --> proteins (oodles)

And remember that in each cell, the particular RNAs and proteins are likely to be very different, since different parts of the DNA are being transcribed.

There are lots of ways to measure expression of RNAs and proteins, both in the animal and (more popularly) in big slabs of jello made from seaweed stuff. Well, it's not really jello but it's a lot like it. You could probably use jello. The idea of the jello (actually called 'gels') is that the different RNAs and proteins get seperated when you squeeze them through the jello with an electric current. You have to seperate them because otherwise it's just a big smeary jumble of stuff, like if all the monk's transcripts were not arranged in orderly little piles ready to count. There's a lot of pants-wetting and hoopla lately about 'DNA chips', which is basically the same science, but it allows one to look at amounts of RNA (and soon protein) from thousands of genes all at once, whereas before you were pretty much a big stud if you did a dozen.


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