Turned up to eleven: Fair and Balanced

Sunday, September 29, 2002


Chimps and Humans, pt II

"Robert Musil" has responded, and then responded again, to my original post. He has proposed some interesting notions, but ones that I think can be largely resolved by recourse to the fundamentals of molecular biology. Now, it seems to me that he is not well versed in the inner workings of molecular biology, which allows him to formulate some very interesting notions about evolution in particular. Nevertheless, I think that my explanation, all compliments aside, perhaps needs a bit of polishing. "Musil" states; (referring to my comments before about "junk" v. "non-junk" DNA similarity)



I think that the "best guess" of a good scientist is worth a lot, and deserves a lot of respect. I also think that a "best guess" is a guess. Further, the proposition that functionality can be expected to constrain genome structure is appealing, as is the corresponding thought that "junk" portions of the genome should be able to drift more.


Two points. 1). I was probably understating the case when I called it a "best guess". There have been many efforts to study human and ape genes, and all have borne out the very close relationship. 2). Functionality certainly constrains genome structure, in highly specific ways.


Moreover, there are plenty of examples of biological systems that serve the same function but seem to have very different structures. For example, the mouse immune system and the human immune system serve the same "function." But the differences betwen the mouse immune system and the human immune system have demolished more than a few immunological theories. It doesn't seem to me to be much of a stretch to ask whether those differences are reflected at the genome level. Of course, primates have more and deeper "functionality" in common than do rodents and humans.

Ah, here is an interesting point. This is, in fact, the core of one of the deepest issues in Molecular Biology, the "structure-function" problem. We know, from years of experimentation, that, within the context of a cell, a given polynucleotide sequence (that is, the gene) gives rise, via several in themselves interesting processing steps, to a single, folded, functional protein (note: I oversimplify, slightly, but getting into alternative splicing would not improve the clarity of this post). A single, folded protein, moreover, has a single function or set of functions. So, given the gene sequence, it is possible in theory to predict the function(s) of a protein. This seems simple, but is in fact incredibly hard, and this single problem has been at the root of biochemistry and mol. bio. research for many years now. We now have very good methods for predicting the "secondary structure" of a polypeptide (there are 4 levels of protein structure), but "tertiary structure is only predicted, at this point, but analogy to known tertiary (often called 3-dimensional or "crystal") structures. But in all of this study, an interesting thing has been found. It appears that there are only a few dozen "folds", that is, general ways that proteins can form 3-dimensional structures. Of course, within each fold there are many variations, but essentially, these proteins of the same "fold" have similar overall shape. So, even though there are essentially limitless polypeptide sequences to choose from (20^n, where n is the length of the sequence), there are very few shapes that seem to work well.

Even more to the point, there are far fewer differences, in terms of the number of genes that vary, between us and, say, corn, than you might think. This is because there is a huge amount of genetic material devoted to "housekeeping" functions. For example, every cell in every organism that exists, or has ever existed, needs to use adenosine tri-phosphate (note to the pedants: very slight exaggeration here, but true in principle). In order to generate ATP, a proton gradient across a membrane has to form. This proton flow across the membrane provides energy to an enzyme that forms ATP. The basis for this process is the chemiosmotic principle, and the overall process is called "respiration". For the purposes of our discussion, the important issue here is that this process is essentially universal, in bacteria, corn, chimps and people. By some estimates, there are several thousand genes in every cell of human bodies that play these sorts of "housekeeping roles. A "simple way" to analyze this is to look at gene expression in different cell types in the body. Every brain, heart, skin, and immune cell contains a large set of genes that simply keep the cell functioning. These genes are a lot less amenable to change than genes for, say, eye color.

So where does this leave us?


But the differences betwen the mouse immune system and the human immune system have demolished more than a few immunological theories. It doesn't seem to me to be much of a stretch to ask whether those differences are reflected at the genome level. Of course, primates have more and deeper "functionality" in common than do rodents and humans.

I think Musil is overstating the case here. In fact, there are tremendous similarities between mouse and human immune systems. Can he name even one "theory" that was "demolished" by the differences? To be sure, there have been drugs tested on mice that didn't work in humans, but that is by no means the same thing. The reality is that the constituents have differences, but the overall function is very, very similar. The more we learn about how the immune system works in general, the better we can understand the observed differences in response.

I think the "mapping fallacy" comments are astute. Biologists do not use this sort of analysis to judge "similarity" in the way that people might judge the similarity of, say, two TV shows. The most important aspect of this, from a working biologist standpoint, is to understand the evolutionary relationship, and to refine our methods for understanding how speciation occurs. To that end, this sort of work is very important.



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