Wednesday, October 24, 2007

Genetics, Epigenetics, and Life

As promised, the overuse of gene post.

I read, on one of my molecular biology binges, that the notion of a gene was becoming increasingly hard to identify. I don't know if I agree with the argument, but here's the general idea. A massive oversimplification of molecular biology says that each DNA sequence is transcribed and translated into a protein, and that each protein has one function. Given that assumption, then there is a one-to-one correlation between DNA sequences and proteins, DNA sequences and functions, and proteins and functions. Hence, a gene is a single DNA sequence, which corresponds to a single protein and a single function (or trait). We can, therefore, isolate the gene for blue eyes, the gene for tall pea plants, and the gene for purple flowers.

However, if we define a gene (as we have done above) as the DNA sequence which is transcribed and codes for the blue-eye protein and causes the phenotype of blue eyes, well, we have a problem. First off, not all of the DNA sequence that causes the phenotype of blue eyes is transcribed. Second, not all of the DNA that is transcribed codes for the protein. Third, not every protein that effects the decision between blue and brown eyes is coded by a single piece of DNA or even effects only that decision. Should things like transcription factor DNA sequences, which are necessary for "turning on" specific sequences and thus for the observed phenotype, be counted as part of the gene? Probably not. But should introns, which are transcribed regions of the DNA that have little effect on activity be counted as the gene? How about promoter regions immediately upstream? Enhancers that can be located long distances removed? The intervening sequences?

No matter how you look at it, it's a mess. Of course, there are rigorous definitions of gene (i.e. coding sequences) but if you use them you leave out the vast majority of the information in the genome (i.e. promoters, enhancers, insulators, microRNAs, other nontranslated RNAs, ...) . The authors of the book I was reading went on to say that, perhaps, the notion of the gene is obsolete.

Of course, I don't follow their final leap of faith that removing the word "gene" from the picture and using only the longer descriptive terms -- enhancer, promoter, coding sequence, exon, intron, etcetera -- would simplify matters. I think it would, if anything, make it harder for any non-biologist to understand what on earth geneticists were talking about. And I am decidedly against making myself harder to understand. But the central point of the argument; that the very idea of a single, isolated gene is an oversimplification and perhaps a fallacy, remains. Genes do not exist on their own. They exist in context and that context is incredibly important to determining what they will do.

In my last post I talked about birds who learn the calls of the birds in the nest where they were raised. That's a typical example of something called epigenetics. That call helps the bird find a mate and eventually find a nest to insert its eggs into, and is therefore heritable, but it is in no way "genetically coded". It can even be the basis of evolution by natural selection: birds who put their eggs into the nests of species who take care of their young well, who find food everywhere and are safe from predators will be more likely to have more of their young survive and therefore will be selected for. But it is not, at base, encoded in DNA and therefore is not genetic.

Epigenetics works at all levels; from the organismal level I've just discussed to levels of gene control and regulation, such as what I'm working on right now. Where a gene is in the nucleus has huge ramifications on transcription and regulation. The state of histones (the proteins that DNA is always wrapped around in the nucleus) creates a "histone code" that is independent of genetic code and controls much of gene activity. These things aren't coded for in the genome, but they are heritable and they do yield phenotypes.

Epigenetics (on both microscopic and macroscopic levels) is a growing field. Scientists are increasingly coming to the conclusion that, well, it doesn't just come down to your genes, even on a molecular level! Yes, I do believe that the entirety of my organism can be described with sufficiently sophisticated chemistry, but also that as a being I am constantly learning and adapting to my situation. I am always making connections between neurons, and those connections make it easier for me to make more connections and so on and so forth. My genes provided a scaffold upon which I could build, but it was only that.

And so whenever someone says that they want to isolate "the gene for intelligence", I cringe a little. Because everything I've just said holds true. The chance that there is a single DNA sequence mediating the immensely complex trait we call "intelligence" is tiny. The chance that there is a single protein mediating that trait is similarly tiny. The chance that we could select for a single gene and therefore raise our intelligence without other, unfavorable side effects is almost infinitesimal. The fact of the matter is that this subtle and complex trait is mediated by an enormous number of variables, from genetic elements to epigenetic ones to cultural ones. And saying anything else is a pathetic oversimplification.

1 comment:

Duff said...

This gets into a part of genetics I have always found interesting, something lacking in the "classical" discussion (high school?) discussion of genes. That is, the feedback and control system that makes genes a viable system to chemically encode the information in our bodies. Control systems can display incredible complication, even with a few simple rules defining the system's response. The other nice view that is afforded by viewing genetics as a control system is the possibility for response to external input and noise. Not everything is legislated a priori, running from a preset program like a simple algorithm, but is a system of feedback and stabilization coping with constant external perturbations. I have begun to suspect that electrical engineering and biology will begin to share more intellectual territory as time progresses. Indeed, biological systems represent perhaps the greatest control systems ever.