Man Without Qualities

Monday, September 30, 2002

More on Our Relative, the Chimp

Paul Orwin of TurnedUpToEleven posts a very interesting (at least to me) continuation of our discussion regarding the significance of studies purporting to show that chimps and humans have similar genomes (with perhaps 95% to 99% of their DNA in common).

Referring to the proposition that comparable "useful" DNA should have more similarity than "junk" DNA, Professor Orwin, among other interesting things, makes 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."

Taking the second question first: of course functionality constrains genome structure. But I don't think that is a correct formulation of the issue. If my questions were put in this form they might look like: "How much does external functionality constrain genome structure compared to internal functionality and other factors?" How can we measure the difference? My questions were: (1) doesn't the 95-99% overlap in non-functional DNA suggest that factors other than external (expressive) functionality may play a major role in determining the structure of this "junk" DNA? (2) In particular, if the "junk" does actually serve some kind of "internal" function, isn't it possible that internal function plays a major role in determining the structure of this "junk."

For example, to look at the simplest case, bacteria have little or no junk in their DNA. Isn't that consistent with a model in which there is no function for "junk" in such a unicellular organism, and that evolutionary pressures have therefore ejected entirely the DNA for which there is no internal structural role (in other words, constrained its "structure" to zero)? After all, I understand that one possible source of "junk" is retroviral insertions - which, I believe, bacteria have to contend with, too. So it's not as if there aren't candidates for "junked up" bacterial strains being produced. They just don't seem to survive.

The link between expressive functionality and genome structure is not, to my knowledge, always so clear as Professor Orwin suggests. For example, there is an immune system receptor common to rodents and humans called CD-32. In rodents it appears to correspond entirely to one gene. But in humans, it corresponds to two genes (CD-32A and CD-32B), but it is my understanding that there are also other ancillary variants of at least CD-32B involved. In this case, there is a lot of difference in genome coding for little or no apparent difference in expressive results (that is, the CD-32 receptor).

I'm not sure what lies between "best guess" (which I already construed as "best guess by an informed, highly competent expert" - and I don't think one generally makes money in Vegas betting against that kind of thing, already) and "scientific fact." But I'll construe this point to mean that Professor Orwin has a high degree of confidence in this guess, and that other experts do, too, and that confidence is probably manifested practically in the direction he and other experts choose for their research. Since to my knowledge nobody has even mapped the chimp genome, I'm not sure how much further one can wisely go at this point, but it's interesting that Professor Orwin is willing to climb out on that particular limb. I am certainly not saying Professor Orwin is wrong, or likely wrong in any of this. My original and continuing focus was on the meaning of the studies that purport to "prove" genome similarities - I don't see any popular articles about what even very good scientists think is probably right, or almost certainly going to turn out to be right, or whatever else may lie between "best guess" and "scientific fact.".

It is certainly well reported in the popular scientific press that various efforts to compare specific human and primate genes have been made, and - at least by the measures described by those researchers - all have borne out very close relationships. Indeed, Professor Orwin cites to one such popular report about a study of the "Y" Chromosome, a report which includes this passage:

The amount of variation in the human Y chromosome, for example, says something about the size of the population from whom we descended. The greater the variety, the larger the starting population must have been. Likewise for the chimpanzees and bonobos. Chimpanzees and bonobos, she found, show significant variety. "I found a ton of variation in chimps and bonobos," she said. Not so with humans, where little variation means we all evolved, recently, from a very small population, a few tens of thousands of individuals less than 200,000 years ago. In that small initial population, the key mutations that made us human could have spread quickly, Stone theorized.

Now, Professor Orwin described this report as a particularly good one supporting his position, but the qualitative language in the above excerpt doesn't seem to have the same confidence he suggests. And while the report does include quotes from the researcher such as: "Chimp and human chromosomes look virtually identical," the details of the report just says the researcher "looked at a stretch of DNA on the Y chromosome," which is hardly enough to determine how extensive the DNA segment studied there actually was. Moreover, the report does not state whether that researcher attempted to isolate a completely "useful;" piece of DNA - although one does get the impression that at least some of the examined DNA was "useful."

What is particularly striking to me about this article is the assertion: "DNA sequences in humans and chimpanzees are more than 99 percent identical .... It is that last 1 percent that makes us human." But as little as 1.5% of all human DNA may be "useful." The Man Without Qualities is not alone in expressing reservations about how meaningful it is to study the "junk": "They say 99 percent of the genome is not genes. I believe it's 3 percent that is genes," said Bill Haseltine, president of Human Genome Sciences.... At any rate, Haseltine believes studying the whole genome is a waste. "It's clear we should focus on genes and not the genome," he said.

In any event, there have been to my knowledge no attempts to simply compare the "useful" DNA of chimps and humans in the aggregate. Indeed, it is my understanding of the current state of molecular genetics that although some pieces of DNA are known to be "useful" there is actually quite a bit to be learned in the area of sorting the "useful" from the "junk." Indeed, there are quite active research efforts underway (including commercial efforts) to find (and patent!) new "useful" DNA concealed within the masses of "junk." So we seem to be rather far from a direct comparision of aggregate "useful" DNA.

I, personally, have difficulty in accepting naked percentages (99% or 95% or whatever) even of "useful" DNA as a very meaningful measure of species similarity. For one thing, as Professor Orwin points out, certain life functions are more basic than others. To use Professor Orwin's example, pretty much every cell in every organism needs to use adenosine tri-phosphate. So why should the presence of the genomic structure that corresponds to the ATP cycle be counted as a very significant point of "similarity" between chimps and humans? The "hedgehog" gene in a fly is considered very similar to the human hedgehog gene, and to the hedgehog gene as it occurs in most animals. Why should that not be a reason for discounting the hedgehog gene as a point of similarity?

If one were to count things like "lights," "desks," "windows," "teachers," "lab hoods," "reagent bottles" and the like at the CalTech biology department one could probably find a very high level of "overlap" with the biology department at "Poly" (the private school that runs through 12th grade down the street from the CalTech department). Would that show that the two biology departments were "very similar"? Isn't there something subtle and different about what goes on in Professor Orwin's head and the heads of his Tech colleagues that gets swamped in all this naive counting ?

Professor Orwin also states:

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?

Well, yes, of course I can. But I'll instead do something which Professor Orwin may find more intriguing: I'll describe a current theory that will soon be demolished in exactly this way. Specifically, there is a "hot" theory stemming from certain assumptions of rodent/human immune system similarities which is hoped in many quarters to have potentially direct application to a certain experimental cancer treatment. That theory will be demolished by a paper soon to be published. The paper will show that instead of the presumed rodent/human similarities at the gene level one species entirely lacks the genes being studied in the other species.

In any event, I hope that Professor Orwin does not find anything I have said above offensive or impertinent. I have been absolutely charmed that he took the time and effort to share his expertise with me, an expertise wildly beyond my own. After all, Professor Orwin could have done what Charles Murtaugh did - link to Professor Orwin and another blog that responded to my original post while refusing to acknowledge my existence, and this although I have permalinked to Charles almost from the inception of this blog. That's fine, everyone has their own view of Blogosphere civility. It's still my best guess that Charles is a wonderful, perfectly charming person.

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