Thursday, December 15, 2005

Is evolution the cornerstone of experimental biology?

The chemist Philip Skell, an emeritus professor at Penn State and member of the National Academy of Sciences, wrote an opinion piece published in the August 29 issue of The Scientist (a subscription is required) titled "Why Do We Invoke Darwin? Evolutionary theory contributes little to experimental biology." I'll get to the substance of the piece in a minute, but the first thing to point out is the misleading title: Why do we invoke Darwin? Skell seems to count himself as a biologist, which he is not. He is a chemist. Perhaps the reactions he studies are relevant to biology, but he is not even a biochemist. As others have already pointed out around the web (like on The Panda's Thumb), Skell has no publications in a journal that deals at all with biology. A PubMed search turns up no articles, and I guarantee you that no scientist who is an authentic biologist or biochemist actually has zero citations in PubMed (unless it is a grad student or technician who doesn't have publications yet).

Skell is not a newcomer to the Intelligent Design controversy (check here, here, and here for starters). I'm not writing this to deal specifically with Skell, but with his general claim, which is heard over and over in anti-evolution circles, that everyday molecular biology/biochemistry/cell biology does not really use evolutionary concepts (another example can be found in this opinion article). The point these people are trying to make is that evolution is in fact not the cornerstone that biologists make it out to be, and that most modern biology could go on just fine without dogmatic invocations of evolution. (Skell calls these invocations just a "coda" or "gloss" on the substance of these papers, and says outright that evolution "does not provide a fruitful heuristic in experimental biology.")

So, what exactly do these critics mean when they say that experimental biology doesn't really need evolution? Obviously, most basic research in biochemistry and molecular biology is not aimed at addressing outstanding questions in evolutionary theory - like the mechanism(s) of speciation, the role of genetic drift, natural selection, and neutral evolution in evolutionary history - because those questions are part of the specific science of evolutionary biology. Biochemists work on, believe it or not, biochemistry, not evolutionary biology. As obvious as this point is, it's clear that Intelligent Design advocates and sympathizers don't get it. That's why ID advocate Michael Behe thinks that by showing the word evolution to be largely absent from biochemistry textbooks, he has demonstrated how superfluous evolution is to the discipline of biochemistry. Phil Skell follows a similar route, by claiming that "[in a review of the literature] I substituted for 'evolution' some other word - 'Buddhism,' 'Aztec cosmology,' or even 'creationism.' I found that the substitution never touched the paper's core." (Leaving the side that as a non-biologist Skell probably cannot actually follow the 'core' of your average biology paper in a journal like Nature, this assertion is simply false regarding the papers I read every day.)

So if biochemists, geneticists, and molecular biologists are not studying speciation, natural selection, or some other aspect of evolution, how does evolution figure into their work as a foundation, or as Skell puts it, a "fruitful heuristic"? The most dominant way evolution figures into basic experimental biology is through homology. Evolution is a complex theory that can't be summed up as a slogan, but if it could, that slogan would be "descent with modification" (and not, by the way, "survival of the fittest"). This slogan captures two important ideas in evolution - that all living organisms descended from a set of common ancestors, and that today's organisms are different from those ancestors.

Biochemists frequently attempt to identify important amino acids in proteins by comparing amino acid sequences of these proteins in a variety of organisms. Thinking in terms of common ancestry and natural selection, we predict that amino acids that are crucial for a particular function are conserved in homologous proteins in many different organisms, while those parts that aren't crucial can vary. Biochemists line up the sequences of a given protein from various organisms, and look for the unchanged amino acids. Those amino acids are predicted to be functionally important; these predictions can easily be tested by mutational experiments. (Take a look at at this example.)

I have an example from some experiments I did just last month. In yeast, there is a membrane protein called Ena5, which is predicted to be a "sodium ATPase" - meaning this protein pumps sodium across the cell membrane by "hydrolyzing ATP", that is, converting a molecule called ATP to a molecule called ADP. This protein is part of a general class of proteins called "P-type ATPases", which are membrane-embedded proteins that hydrolyze ATP in order to pump something across a membrane.

To my knowledge, nobody had actually tested Ena5 biochemically, but we were pretty confident about the prediction because Ena5 has a set of amino acid sequences that are the same or very close in all proteins of this class (each letter stands for an amino acid):

1)LDGES, 2)SDKTGTLT, 3)KGAFE, 4)MLTGD, 5)GDGVND (taken from Catty, et al.)

Ena5 consists of 1,091 amino acids, most of which which differ from other ATPases, but those 29 amino acids I listed are closely conserved. Why? Evolution explains why - these portions are functionally important, and thus natural selection preserves them. But it is important to note that this is not the only way to build a sodium pump; you can build one without the sequences I listed above. These particular sequences are conserved because an ancestral sodium pump just happened to be built a certain way, and from then on, natural selection preserved those sequences.

Using this idea, that natural selection preserves important residues, we had a pretty good idea that Ena5 was a sodium ATPase without even testing it. And sure enough, when I tested this protein's ability to hydrolyze ATP, it worked. (Reconstituting the actual sodium pumping activity is more complex experiment, but will probably be done if we follow up on this particular protein.) Using evolutionary reasoning, we can make predictions that are useful in the biochemical study of proteins. This type of reasoning is absolutely crucial to our understanding of human biology - we can do experiments in yeast that we can't do in humans, and without the study of homologs it would be nearly impossible to identify proteins with a given function in the human genome. Biochemists and geneticists do this all the time. This is not just gloss - without the concepts of evolution, these functional predictions would make absolutely no sense.

I've droned on enough, but this is just one example of how evolutionary reasoning is used in everyday biology. There are many others.

2 comments:

Ricardo said...

Dr. Michael, I'm very surprised that somebody with 691 hits on PubMed would state that Dr. Skell has no work published there, when even I, a college drop out, managed to find the work Dr. Skell himself hints in his article:

"Certainly, my own research with antibiotics during World War II received no guidance from insights provided by Darwinian evolution."

Assay of Streptomycin by the Paper-Disc Plate Method.
PMID: 16561049 [PubMed]

* Loo YH,
* Skell PS,
* Thornberry HH,
* Ehrlich J,
* McGuire JM,
* Savage GM,
* Sylvester JC.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16561049&query_hl=1&itool=pubmed_docsum

Evolutionists seem to get religiously blinded when arguing Evolution.

Mike said...

Uh, even as a college drop out, you ought to be able to figure out that all 691 hits you found on PubMed are not from the same Michael White. I currently have one published paper, and one manuscript in press.

Anyway, the fact that I missed one Skell citation from the 40's doesn't change my claim that Skell is not a biologist, nor does it support your nonsensical claim that I am "religiously blinded when arguing evolution."

FYI, until fairly recently, PubMed didn't any cover citations from before the mid-50's, and they are currently adding a lot of older citations daily. When I did my original search for Skell articles back in December, I got no hits.