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more to a genome than a string of nucleotides

It's always bothered me to hear statements along the lines of 'now that we now the genome of [insert species name here], we know all about [insert species name here].' That's so far of the mark, because there is more to the genome than the string of As, Ts, Gs & Cs that make it up. Beginning his post on this issue, PZ Myers says

We miss something important when we just look at the genome as a string of nucleotides with scattered bits that will get translated into proteins — we miss the fact that the genome is a dynamically modified and expressed sequence, with patterns of activity in the living cell that are not readily discerned in a simple series of As, Ts, Gs, and Cs. What we can't see very well are gene regulatory networks (GRNs), the interlinked sets of genes that are regulated in a coordinated fashion in cells and tissues.

What this means is that if you look within a specific cell type at a specific gene, its state, whether off or on, will be correlated in a coherent way with a set of other genes. Look in a developing muscle cell, for instance, and you'll typically find a gene called MyoD is switched on, and also other genes, like Myf5 and myogenin. Look further, and you'll find others like C-jun and cyclin-dependent kinase 4, that also have their activity modulated in predictable ways. And when we start poking around experimentally, we discover that the relationships are often directly causal, with certain gene products binding to and modifying the expression of other genes.

You should read on, because he then goes on to explain how all this is done.

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3 Comments

Alison, is this any more complicated than figuring out what a computer program does by looking at its code? I was a programmer 20 years ago and then went off to law school and a fascinating practice... but now I'm back into running my own business and have to put on my programming hat again. That means I've had to crack open some "open source" software and figure out what it's doing so I can make changes.

To make a SMALL change to my ZenCart store, I had to learn what "classes" are, find the "class.php" file, dig out the "default_header.php" file, and go look into a MySQL database to read a parameter. All this assumed I already knew how to program in php (which I didn't), and it leaves out all the optional language files I didn't bother with.

My point is--software can be scattered all over the place (it can even be scattered all over the internet!) and still work. It doesn't seem to me that genes should present a fundamentally more difficult challenge. It's just that NONE of us know how to "program" genes yet, so we're having to reverse engineer it all as we go.

Yes, it is more complicated - because epigenetic modifications are not part of the code - ie you're not just looking at 'a string of nucleotides'. This is why I've never liked the reductionism implied in the view that once we have 'the' human genome we know all there is to know about how people work. That is a very long way indeed from reality.

The comparison with examining computer code doesn't hold.

Even leaving out epigenetics, a huge difference compared to computer code is that you can read computer code and know what it does. ("If I load these variables with these values, this is what will be returned".) Computer programs can be reverse engineered by merely looking at the code. Genomes can't. With a genome (DNA) sequence on it's own you haven't the foggiest idea what any part of the DNA does. As PZ Myers was saying you can't see the gene regulatory networks from the DNA sequence; as he explained these are determined experimentally by observing what happens in living cells. (Note the "scattering all over the place" you refer isn't the point he was making.)

Even comparing DNA sequences in itself doesn't tell you what a gene or other region of DNA does. What makes comparisons "work" is that a some point a "match" to a gene (or regulatory region, etc.) whose function has been worked out from studying living cells and you can infer it's possible function from this. (You can't confirm it until it's been experimentally verified, either.) It's the studying living cells that gives you the functional information.

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Recent Comments

  • Grant: The comparison with examining computer code doesn't hold. Even leaving read more
  • Alison Campbell: Yes, it is more complicated - because epigenetic modifications are read more
  • Scott W. Somerville: Alison, is this any more complicated than figuring out what read more