Monday, 2 July 2012

Addition of Genetic Information Redux: A Critical Response to a Critical Response


A few years ago ( when my blog was a bit more active than it is today) I wrote up a post rebutting the old creationist canard that evolution requires "new" genetic "information" to be added to a genome, and, furthermore, that such a process is impossible and consequently, evolution is false. Recently, a LiveJournal user by the name of Jair_greycoat wrote up a response to my article. After reading it, I think that there are a number of points that I should clarify and some misconceptions that should be corrected. Such a task is too much for the LiveJournal comment section, so I've written up my reply to the criticisms below.

"Why would creationists claim that beneficial mutations are rare or impossible? Didn't the author of the above quote just provide a real, observable example? The only claim I have heard from creationists regarding this is that all, or nearly all, such beneficial mutations are a result of a loss in information, not a gain. I have not personally heard them claim that the loss of information cannot be helpful. We do have a saying, "ignorance is bliss." If a person's body is "ignorant" of alcohol, then they have "bliss"--they can't get drunk, or so I've heard. Nevertheless, the author of the quote agrees with the creationists that the mutation is a loss of information."

Why would Creationists claim such a thing? Your guess is as good as mine. The scientific literature is replete with examples of mutations which confer a beneficial or improved phenotype. The classic example of sickle-cell anaemia is one, as is lactase persistence in European populations (see here and here). Creationists, nonetheless, are not always ones to let reality get in the way of their religious beliefs, and routinely claim that beneficial mutations do not – and cannot – occur. The argument is quite common in the Creationist literature; see this article from Creationstudies.org for example, "The Myth of Beneficial Mutations", which outright claims "The bottom line is that mutations always weaken an organism". Other examples of this can be seen here and here and here. The claim comes up so often that even Answers in Genesis had to tell people to stop using it.

The claim that beneficial mutations only come about by a loss of information, as you mention, is another claim that comes up - one that is equally false. The example of sickle-cell anaemia as mentioned above is not due to a "loss of information" (which I take as to mean a deletion in a gene) but rather due to a change in a single nucleotide in the gene – from an A to a T. This change results in a protein that is altered in one amino acid, and confers resistance to malaria. Another example is the evolution of lactulose metabolism in E.coli, which occurred not through the "loss of information" but rather from a genetic recombination within a previously existing gene; that is to say, the "information" (for the lack of a better term) was rearranged and gave rise to a novel, beneficial function. Or how about this interesting example: some placental function in vertebrates is due to a proviral gene that is integrated into our genome – again, a gain of genetic "information", rather than a loss of it. The point I'm trying to make is that for every example you can point to where a beneficial phenotype has arisen due to a genetic deletion, you can also point to one that was caused by a gain of "information".
 
It is one facet of this "gain of information", namely diversification of gene function via genetic duplications, that the rest of my article aimed to address. The creationist claim I was rebutting was that a "gain of genetic information" is impossible, and I went on to provide a mechanism whereby it can occur.

"The author then says that the term "information" is too vague and not defined by creationists. Personally I've never had a problem with the word, I think it means exactly what it sounds like it means."

Perhaps he does not realize that the word "information" has multiple specific meanings in science. When a creationist mentions "information", are they meaning actually physical information? In which case, are they referring to classical information or quantum information? Or maybe they mean information in the technological sense, as in "instructions" or "code"? A loss or gain of "information" takes on very different meanings depending on which sense of the word you're using. "Information" is a rather clumsy word to use when describing genetics for this reason, and it is not used widely in the biological community. Its use in reference to genetics seems to be restricted to Creationists.

"Why would creationists claim that genes are never added to a genome? Of course genes are added; I think we can agree on that. What I have heard creationists deny is that these new genes contain new and original content, or that they are capable of transforming into new and original content that is not simply random garble."

See above. Creationists claim that because they are either ignorant of the facts or refuse to accept them.

"Now I realize that the writer is probably using the words "gene" and "information" interchangeably."

Again, refer to my explanation of the problems with using the word "information" above. I used "information" throughout my original article because it is the term that Creationists throw around all the time. I use it in quotes to show that it is an ill-fitting word be using in such a context. I used "information" to refer to both genes and gene sequences, since that is what I think Creationists mean when they throw the term around.

"Then the author goes on to quote Ross Hardison. As I see it, the quote is essentially a hypothesis about the evolution of a haemoglobin gene. I don't have any questions about it except this part: "In this way, the two genes that started out identical acquired sequence differences and later, functional differences." But how do these mutations become functional differences rather than just causing everything to fall apart, as I would expect from entropy?"

To answer this, you must really think about just what a mutation means to the gene it's situated in. A mutation, whether it is a deletion, addition or just a change in the sequence, carries with it the risk of altering the sequence of the protein for which it codes. Proteins get their function from their shape, and their shape is directly (more or less) determined by their amino acid sequence. As mutations accumulate in a duplicated gene, the chance of these mutations altering the function of the protein it encodes rises. Of course, it is not guaranteed that these alterations will be of any benefit, but that's where natural selection plays a role. In those instances where the mutations are harmful, the gene is less likely to be passed on. Those that confer some benefit are more likely. In this manner, over generations, the net effect becomes a positive one. When we look at the haemoglobin gene today, we're looking at it with a bias – we only see the mutations which were passed on through the generations and not the harmful ones that were weeded out. 

Have you ever played the game Yahtzee? In that game, you have to roll five dice, and you're scored based on the combination of numbers that result. The best score you can get on a turn – the eponymous Yahtzee – is to get a 6 on all five dice. The chances of getting a Yahtzee are pretty low, only 1 in 7776. But the game lets you roll the dice three times, and you're allowed to select the dice you want to keep between rolls. So if you roll 6 on two dice on your first attempt, you can keep those and only roll the remaining three on your second try. In this manner you greatly increase your chance of scoring a Yahtzee; it now becomes 1 in 22 (see here if you're interested in the math behind it). Natural selection works in exactly the same principle. The odds of getting a beneficial new function out of random mutations is low without selection. But selection allows those good mutations to be saved and the bad ones to be discarded. Once you apply selection, novel functions can arise quickly and easily. 

I should also point out here that even a loss of function or a reduced function is still a functional difference. Any mutation that is not neutral or silent, by definition, results in some functional difference. The question, then, should not be "how do mutations become functional differences" but rather, "how do these mutations result in something that is beneficial rather than deleterious", the answer to which is natural selection.

One other point that I would like to make before continuing is regarding the author's use of the word "entropy". I have seen this word tossed about by Creationists more times than I can count, and in almost all the cases, they are not using the word in the correct sense. Creationists are often quick to cite the Second Law of Thermodynamics as "Over time, the amount of entropy in a system increases", and then claim that evolution violates this principle as it requires that over time, entropy must decrease, viz. genomes becoming more ordered rather than degrading into non-coding gibberish. The Second Law of Thermodynamics is no obstacle to evolution, however, as the definition of the law cited by Creationists leaves out a pivotal point: that it applies only to a closed system, that is, a system where there is no flow of energy into or out of it. Biological systems are, of course quite open, with energy flowing freely into and out of them. Genomes are under no obligation to fall victim to increasing entropy. 

"Again from the main article, I quote: "I can already hear the cries of the creationists. "But," they proclaim, "this doesn't show evolution at all, for the different haemoglobin genes are still all the same kind!" (Oh how I hate that dreaded "kind" word)." I'm going to step out and say that I have never heard any serious creation-scientist speak or write a sentence like that one. It does not even make sense in context. Why would a creationist talk about "kinds" with regard to genes in the first place? "Kinds" as far as I have heard it used, is a word used by creationists to refer to different species. It would make more sense, I think, if the sentence was written as: "But," they proclaim, "this doesn't show evolution at all, because it is only a story which doesn't explain the fundamental difficulty! How can random mutations produce meaningful structures which help a species' survival?""


I cannot comment about how familiar the author is with the claims of "serious creation-scientists" but the "kind" argument is one that I've heard a mindboggling number of times. It seems to be a favourite of Kent Hovind and Ken Ham. They argue that "no dog ever gives birth to a cat" (which, if it occurred, would be a blow against evolution, not in support of it) and that's because dogs are one "kind" and cats are another "kind". The major problem with the "kind" talk is that Creationists never use the word in a consistent manner. The author claims that they use "kind" synonymously with "species", which is blatantly false. Are "dogs" and "cats" species? Creationists will claim that Drosophila melanogaster is a "kind", but also that flies in general are a "kind". They use the word to refer to whichever biological taxon is convenient to them at the time, whether that be a species, genus, family or other taxon. It is in this sense that the hypothetical Creationist response that I proposed makes sense. The haemoglobin example I used show how new, but similar, haemoglobin genes evolved. The likes of Ham and Hovind would classify these as the same "kind" in the same way they classify dog breeds as "kind" (note that I'm not saying that such a comparison is justified, only that it is one that I imagine Creationists would make). The remainder of the paragraph the author quoted then went on to explain how new different functions can arise.

"The article explains that new structures--new content in the genetic code--can come from numerous mutations over time. Bad mutations would be weeded out by natural selection, and good ones kept. This made sense to me--on the surface--collect enough mutations over enough time, and there is the possibility of hitting a combination containing survival value simply by chance. I'll try to explain why I think it doesn't make sense on a practical level later in this entry."

Here the author demonstrates that he does understand the process of natural selection, if only superficially. This makes me wonder why he seems to have difficulty understanding how this principle can be applied to duplicated genes evolving novel functions.

"I don't know exactly what percentage of mutations creationists claim are harmful. However, isn't any mutation that isn't beneficial, a potentially harmful one? Especially when you have a large number of mutations, each being by itself neutral or nearly so; but when many such mutations pile on, it doesn't matter--the overall original function of the gene is destroyed, because it no longer contains the original instructions for whatever structures it previously needed to survive...Why would only one of the copies be mutated? Wouldn't both of them mutate at the same rate?"


As mentioned above, Creationists alternately claim that all mutations are harmful, or that most mutations are harmful. The reality is that the vast majority of mutations are neither harmful nor beneficial. Most mutations are neutral, that is to say, they have no affect on the gene at all. Since the genetic code is redundant (i.e. there are many nucleotide codons which code for any given amino acid), most mutations won't affect a protein's sequence at all. Furthermore, similar codons code for amino acids that are chemically similar, so a mutation that does alter the protein sequence will not necessarily alter the protein's function. These neutral mutations confer no advantage or disadvantage on an organism and are therefore invisible to the eyes of natural selection. If a gene were to acquire a large number of neutral mutations, it's affect on the gene would be minimal precisely because they are neutral! The original function of the gene would not be destroyed at all. 

As for mutation rates: yes, it would be safe to assume that both the genes would have the same mutation rate. However, it has little bearing on the ultimate fate of the genes. The reason we see many more mutations in one copy of the gene and not the other is because a deleterious mutation in both copies could prove lethal. Any organism that had both copies mutated in such a way would die and those versions of the genes would not get passed on to successive generations. However, it that same deleterious mutation occurred in one copy and not the other, this would not affect the organism since it still has an original, functional copy remaining. The other copy is free to accumulate mutations as long as there is still an original, functional copy remaining. 

"But in order for a mutation to be considered helpful to a creature's survival and therefore selected by nature, doesn't it have to be part of a fully functional structure from the very start? If not, in what way is the mutation helpful? I believe that even if the mutation is comparable to the first steps in building a genetic program, until that program is finished and complete, it will be a drain on the organism's resources, and therefore harmful. I should think then, that even mutations that could in the future be beneficial (those that are not merely losses of information) would be weeded out by natural selection. Hence why the article I quote from does not make sense to me in this respect. "Fundamentally, this type of evolution requires natural selection to step into the picture and choose between variations--which organism is most fit. But isn't natural selection a blind process? At least according to atheists, I have heard that it is. How can a blind process select for mutations that have the future potential to be part of new functions and structures, yet have no survival value (or worse, are a net drain on the organism) in the present?"


What the author presents here is his own version of the Irreducible Complexity (IC) argument. "What use is half a wing?" the argument often goes. The examples that are usually brought up – the eye, the bacterial flagellum – have been debunked countless times. I could write an entire blog entry on the problems with the Irreducible Complexity argument, so forgive me for being terse here. The major flaw in IC is that it does not account for the gradual adaptation of one biological system for a different, novel function. What good is half a flagellum to a bacterium, you ask? Well, it works great as a Type III Secretion system. Sure, if you removed any of the flagellar components, it might cease to function as a flagellum. But that ignores the fact that the "half a flagellum" may have some other evolutionary adaptation entirely. This can be said of any supposedly "irreducibly complex" system. Interested readers can read more about the problems with the IC argument at TalkOrigins.

"If by "no new genetic info" the author means "no new and original content" rather than copies of previously existing genes, then the reason the claim is so common is because (as far as I know) there is no explanation from evolutionists as to how new and original information can come from mutations and natural selection."


If this is the case than the author has either misunderstood the mechanism that I have described in my article or is unfamiliar with the criticisms of Irreducible Complexity. Again, I refer to the TalkOrigins article I linked to above.

"What about the creation-scientists who are also part of the scientific community and who probably say quite loudly that gene duplication is not a sufficient mechanism for evolution? This quote just feels like the author of the article is intentionally ignoring them. This probably bothers me even more than the article's explanation for gene evolution, because it seems to imply that the author, at some level, does not see creation-scientists as "real scientists". That is just wrong, especially as I have seen plenty of books written by them, and those which I read made plain and simple sense to me. Certainly more sense than the article I quote from made."

The author does get this one thing correct: I don't consider "creation-scientists" to be real scientists. If the author has any particular individuals in mind who he feels are real, practicing scientists, I would love to know who they are. But for the most part, "creation scientists" fit one or more of the following descriptions:
  1. Do not have a degree in a scientific field related to evolution (evolutionary biology, molecular biology, etc.).
  2. Do not have a degree from a recognized, accredited institution.
  3. Do not publish actual research in peer-reviewed scientific journals.
Unfortunately, if they do not match these criteria, then they're not real scientists. It might sound harsh but that's the way science works. Again, if the author has literature from a scientist who holds a relevant degree from an accredited institution that has been published in a peer-reviewed journal, I'm all ears. But until then, I'll give "creation scientists" all the credit they deserve; which is to say: none.

Monday, 5 March 2012

Another Daily Dose of Science Journalism Fail

Care of The Telegraph comes this sensationalist little blurb:


If the fact that the "earliest human ancestor" is eel-like doesn't push your incredulometers into the "Something Isn't Right Here" zone, then consider this line from the article: 
"Fossils dating back 505 million years preserve the relics of tiny, slithering animals which are the oldest life forms ever discovered with primitive spinal cords.
As the precursor of vertebrates the species is also believed to be the direct ancestor of all members of the chordate family, which includes fish, birds, reptiles, amphibians and mammals."
Ah, well, that makes much more sense! But, that means the headline is incredibly misleading. This fossil is not simply the ancestor to humans, it's the ancestor to all chordates! That includes bats, bears, dogs, cats, aardvarks, aardwolves, all manner of fishes, frogs, salamanders, dinosaurs, eagles, parrots, rats, mice, koalas, kangaroos, bison, pigs, goats....you get the idea. Yes, Chordata does include humans, but it includes anything with vertebrae (and some things without them).Calling this the "earliest human ancestor" is yellow journalism, as far as I'm concerned. That's not to say that this finding isn't interesting. It is! But to define it in the context that the The Telegraph has done is misleading and sensationalist, and only further drives my conviction that science communication should be left to the scientists.

Thursday, 19 January 2012

What do insects, plants and skepticism all have in common?

They all converge into one singularity of awesome over at Botany, Bugs and Bunkum. It's a new blog, set up by a good friend of mine. If you're interested in any of the aformentioned subjects then I highly reccomend checking it out!

Wednesday, 18 January 2012

A Dispatch from the Science Writing Wars

From Ed Yong's blog Not Exactly Rocket Science, comes this infographic that pretty much sums up the Scientist vs Science Journalist debate neatly:


Monday, 3 October 2011

A Noble Prize and a Noble Conundrum

Today the 2011 Nobel Prize in Medicine/Physiology was awarded. This year's Laureates are Bruce A. Beutler and Jules A. Hoffmann for their discovery of how innate immunity is activated, and to Ralph M. Steinman for his work on how dendritic cells are involved in adaptive immunity. Congrats to all of them!


But there's a conundrum here. Steinman, unfortunately, passed away on September 30th. The winners were chosen last week (they are officially announced a week later), and three days later, Steinman died. This presents a problem for the Nobel committee, because the awards are never given out posthumously. Should Steinman still be awarded the prize?


I would say yes, and I have a feeling that the committee will make the same decision. Steinman was still alive when the decision was made to award him the prize, and it was only afterwards that he passed away, before the official ceremony. I think that it's likely that the award will be accepted by someone in his place, and Steinman will have the distinction of being the only person to - technically - receive a Nobel posthumously.

Friday, 30 September 2011

Nobel Prizes 2011

This Monday (October 3rd) marks the beginning of Nobel Prize season. The prize in Medicine/Physiology is awarded on Monday, with Physics on Tuesday and Chemistry on Wednesday (the Peace prize is awarded on Thursday but who cares about that one?)1.

Any guesses on who will be the lucky Laureates this time around?

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1. No date, as of writing, has yet been set for the prize in Literature. I have not included the Economics prize in this list because it isn't a real Nobel Prize, despite popular opinion that it is.

Techniques in Molecular Biology: Monoclonal Antibody Production

Antibodies are perhaps one of the most important tools in the arsenal of molecular biologists. They have a wide variety of applications, from targeting macromolecules with fluorescent dyes or other indicators to aid in visualization, or as a component of other molecular techniques, such as immunopercipitation of proteins. Antibodies that specifically target a researcher's molecule of interest, though, have not always been in the biologist's toolbox.

Before researchers had this ability, antibodies were produced using a simple technique: inject your antigen of choice into a mouse (or goat, or rabbit), and the mouse will produce antibodies targeted against the antigen. After taking a blood sample from the mouse and collecting the serum, the antibodies could be purified. Antibodies produced in this manner were said to be polyclonal: that is, they were derived from multiple antibody producing B-cells in the spleen. Each antibody producing cell produces a different antibody1, and antibodies produced in this way will be a mixture of different antibodies from different cells.

Monoclonal antibodies, in contrast to the polyclonal variety, are derived from a single antibody producing cell. Antibodies from a single cell will all be specific for the same antigen epitope. This confers several advantages over polyclonal antibodies. Perhaps the biggest advantage is that they allow researchers to target specific epitopes on an antigen. Let's say you wanted to mark a specific residue on a protein using antibodies that are labelled with a fluorescent dye. Using polyclonal antibodies, your protein would end up labelled all over, since the polyclonal antibodies would bind of a variety of epitopes on the protein's surface.  Monoclonal antibodies specific to the residue of interest would get rid of all the problematic non-specific binding.

The production of monoclonal antibodies, however, is somewhat different, and pretty cool. The technique starts off just as it would if you were making polyclonal antibodies: inoculate a mouse using your antigen of interest. The antibody producing B-cells in the mouse spleen will begin to make antibodies that target your antigen. Where Köhler, and Milstein's technique differs is in what is done with those B-cells. Normally, the antibody-producing cells only start making antibodies near the end of their life. Isolating individual cells (thus isolating only one type of antibody) and growing them in culture would work to produce monoclonal antibodies, but only for a short amount of time. Milstein and co. got the idea of fusing the B-cells with immortalized mylenoma cells. Cancer cells can, for a variety of reasons, become immortalized2, and continue replicating - indeed, this is what makes cancer a problem! By creating hybrids between B-Cells and mylenoma cells - called hybridomas - they were able to created antibody-producing cells that live forever and keep on producing antibodies. Culturing these cells and purifying the antibodies now became a more viable option. Separate cell lines were isolated and cultured, so that each culture contained only cells from an individual lineage, and consequentially, produced only one kind of antibody. These cells are first grown on plates to establish a lineage, but are eventually transferred to large tissue culture flasks. This allows for tons of monoclonal antibodies to be produced, isolated, and used by researchers the world over.

This technique pioneered by  Milstein and Köhler revolutionized the way research is done in molecular biology.  It was important enough that it won Georges Köhler, and César Milstein, the Nobel Prize in Medicine in 19843. Since then, antibodies that target any antigen imaginable have been developed, and can easily be ordered from companies that specialize in production of monoclonal antibodies. It is unlikely, I think, that monoclonal antibodies will be ever displaced as a staple tool for molecular biology research.

FURTHER READING:

I you're interested in reading more about the history of antibodies, their discovery and the story of Milstein and Köhler's work, I suggest reading through "A Brief History of the Antibody" posted at the Proteintech Group blog [Part I Part II Part III]. Milstein's Nobel lecture also contains some interesting insights into antibodies, antibody research and the development of Hybridoma technology, and can be found here.


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1. The different antibodies produced are specific for the same antigen, but are directed towards different epitopes on the antigen.

2. This is to say that they are not subject to the Hayflick Limit. The Hayflick Limit, named after American researcher Leonard Hayflick, is the number of times a given cell line can divide before stopping. Originally, cells were thought to replicate indefinitely, and failure to keep cell lines alive was thought to be due to ignorance of optimal techniques. Hayflick and Paul Moorhead, working at the Wistar Institute in Philadelphia in 1961, showed experimentally that cell lines impose a limit on the number of times they can divide. The limit differs between cell types, but for humans it is around 52 divisions.

3. The prize was shared with Neils Jerne, who was awarded the prize for his work on the development and control of the immune system.

Friday, 9 September 2011

Rick Perry and Galileo: BFFs?

With the impending doom that is the Republican presidential nomination looming ominously on the horizon, Wednesday was the night of the latest debate between the Republican candidates. On the list of talking points was the inevitable question about global warming. Denying global warming is de rigueur in the Republican party these days, so it wasn't surprising that, with the exception of Huntsman, the idea of anthropogenic climate change was scoffed at across the board. It was Rick Perry, though, that did manage to raise some eyebrows when he delivered this gem:
"The science is not settled on this. The idea that we would put Americans' economy at jeopardy based on scientific theory that's not settled yet to me is just nonsense...just because you have a group of scientists that have stood up and said here is the fact, Galileo got outvoted for a spell."
Oh, Rick, you silly man. How art thou wrong? Let me count the ways:

1) The science is settled on the issue. Anthropogenic climate change is a reality, one that is accepted by the vast majority of scientists. Some of the exact particulars of the issue are currently under debate - long-term climate projections for the future, the extent to which particular pollutants have contributed, etc - but these are not the things that Perry claims are unsettled. It is the mere existence of anthropogenic climate change that Perry denies, and as far as science is concerned, that issue most certainly is settled.

2) Galileo was not "outvoted". Perhaps this was just a bad choice of words on Perry's behalf, but I fear that it indicates a deeper misunderstanding of how science works. Scientific debates are not settled by a vote. Scientists are not polled for their opinions and the ideas of the majority put forward as the scientific reality. The "truth" is not determined by popular vote, but by careful and critical consideration of the evidence. I'd like to think that Perry realizes this, but given the anti-science attitude that he and many others in the Republican party display, I'm not so sure that he does.

3) Does Perry not realize that Galileo's ideas were not suppressed by the scientific community, but rather, by the Church? Perhaps, as a religious conservative himself, Perry has chosen to overlook this fact. Galileo's case does not parallel the criticisms against climate change denialists. Galileo did not meet resistance from the scientific community, for one. The heliocentric model was supported by a large number of Galileo's contemporaries, including Copernicus (who was the father of modern heliocentrism!), Johannes Kepler, and to some extent Tycho Brahe (who had posited his own heliocentric model of the solar system). The condemnation of heliocentrism came from outside the scientific community. It raised the ire of the religious community (much like the concept of global warming does today!). Compare this to climate change. Climate change "skeptics" do not form a large portion of the current scientific community and are largely found on the fringes of science and often in disciplines unrelated to climate change. They are criticized by the scientific community itself, and this in no way parallels the persecution experienced by Galileo.

Friday, 22 July 2011

Researchers discover "7th and 8th bases of DNA"? Hardly. Here's your daily dose of science journalism fail.

Making the rounds on the blogosphere and the news sites today is the announcement that researchers have discovered the "7th and 8th bases of DNA". This announcement comes from a paper published online on Science's pre-print server1, Science Express by researchers at the University of North Carolina School of Medicine, and most of the news reports seem to be based on an article posted to Science Daily. The article reads:
"For decades, scientists have known that DNA consists of four basic units -- adenine, guanine, thymine and cytosine. Those four bases have been taught in science textbooks and have formed the basis of the growing knowledge regarding how genes code for life. Yet in recent history, scientists have expanded that list from four to six. Now, with a finding published online in the July 21, 2011, issue of the journal Science, researchers from the UNC School of Medicine have discovered the seventh and eighth bases of DNA."
Oooh! Exciting! What are these bases, exactly?
"These last two bases -- called 5-formylcytosine and 5 carboxylcytosine -- are actually versions of cytosine that have been modified by Tet proteins, molecular entities thought to play a role in DNA demethylation and stem cell reprogramming."
So, wait a second. These "new" bases are only modified forms of cytosine? So what? This is no big deal at all. There are well over a dozen known modified bases. Here, let me list a few:
  • 5-hydroxymethylcytosine
  • 5-hydroxymethyluracil
  • N4-methylcytosine
  • 7-methylguanine
  • N6-methylcytosine
  • β-D-hydroxymethyluracil
Need I go on? If we're counting modified bases, then there are perhaps two dozen or more known bases. Why do 5-formylcytosine and 5-carboxylcytosine get the elevated status as the '7th and 8th' bases, when there are so many more modified bases that seem to have gone ignored (and who, for that matter, gave 5-methylcytosine and 5-hydroxymethylcytosine the distinction of being the 5th and 6th)?

Is the discovery of 5-formylcytosine and 5 carboxylcytosine interesting and exciting? Yes, most definitely. Are they the "7th and 8th" bases of DNA? Nope, not at all.

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Ito, S., Shen, L., Dai, Q., Wu, S.C., Collins, L.B., Swenberg, J.A., He, C., and Zhang, Y.  Tet Proteins Can Convert 5-Methylcytosine to 5-Formylcytosine and 5-Carboxylcytosine. 2011.  Science Published Online 21 July 2011 doi:10.1126/science.1210597

Friday, 15 July 2011

Of Hens Teeth and IDiots.

The literature published by the Discovery Institute often confuses me. I'm never quite sure if it should frustrate me or amuse me. Their constant mangling of science combined with their propensity for telling half-truths and distorting reality both makes me laugh (hah! They really think they have science on their side?) and makes me embittered (How dare they twist science to deceive and miseducate?). I guess this recent article by Discovery Institute crony Casey Luskin should be of no surprise, then. In the piece, titled Of Hen's Teeth and Neutral Mutations, Luskin attempts to dismantle a claim made by Stephen Jay Gould about hen's teeth (or the lack thereof):
"Evolutionists often cite an experiment which purportedly induced tooth growth in chickens, supposedly confirming that birds have genes for teeth and are descended from toothed reptilian ancestors. For example, in his book Hen's Teeth and Horse's Toes, Stephen Jay Gould discusses this experiment...But there's a problem with Gould's argument: as Sean Carroll explains, neo-Darwinism has a 'use-it-or-lose-it' rule. According to neo-Darwinism, if a trait is not used then the DNA which encodes it will accumulate neutral mutations, and eventually the trait will be lost forever. If supposed chicken genes for producing teeth haven't been used for 60+ million years, then that would strongly suggest that neutral mutations should have long-since destroyed their ability to function."
For those of you who might be unfamiliar with the experiment in question - and with Gould's discussion of it - it would be worth the while to go into detail.  In 1980, Gould published the book Hen's Teeth and Horse's Toes, a collection of articles he had written for various magazines (primarily for Natural History). Included was an article of the same name where he discussed atavisms - apparent reversions in individuals to an ancestral phenotype. Gould claimed that atavisms are a shining example of the evolutionary past of a species coming to the surface. He illustrated his point with two examples: polydactyl horses and chickens with teeth. It is this second example towards which Luskin has aimed his bow and launched forth a volley of ignorance.

On p.1821, Gould explains a curious experiment performed by E.J. Kollar and C. Fisher: they devised a way to prompt chickens to develop teeth. If it's been a while since you took a good look in the mouth of your local avian friends, then it might interest you to know that birds don't have teeth. The most recent known fossil of toothed birds dates to around 80 million years ago, so somewhere in the intervening time, birds lost the ability to produce teeth. Odontogenesis in vertebrates is a complex process (then again, developmental programs always are!). It requires two different tissue types to occur: epithelial tissue and mesenchyme. The outer enamel layer of a tooth is formed by the epithelial tissue, while the inside dentin later of your tooth grows from the mesenchyme. But there's a catch: the mesenchyme cannot produce dentin by itself, it needs to be in contact with epithelium for dentin production to begin - that is to say, epithelium induces the production of dentin. This dentin, in turn, induces the production of enamel in the epithelium. Birds don't produce dentin, nor, consequently, enamel, so birds are born toothless. Kollar and Fisher's idea was brilliant but simple: what happens if you graft chick epithelium with murine (mouse) mesenchyne? Mice most definitely have teeth, so we know their mesenchyne is capable for producing dentin if prompted by epithelial tissue. What they found was astounding: when mouse mesenchyne was grafted to chick epithelium, teeth (dentin and all) were produced. This meant that avian epithelial tissue - despite the fact that birds have no teeth, and have not had teeth for as long as 80 million years - is still able to induce dentin production in the appropriate mesenchyne. Gould mused that this experimental result displayed the evolutionary history of birds. Why else would avian epithelial tissue have the latent ability to induce dentin production unless they had descended from toothed ancestors?

Luskin, however, thinks that Gould was completely wrong. Luskin argues that, if birds lost the ability to produce teeth 80 million years ago, then the genes for tooth production would have accumulated so many mutations that it would be impossible to revert back to the original toothed phenotype. The tooth production genes, he claims, would have since been destroyed beyond the ability to function. He bases this argument in something called Dollo's Law. Dollo's Law, put simply, states that evolution cannot reverse itself, and that genes which escape selection pressure will degrade fast enough that reverting to the original phenotype is tantamount to impossible. According to Luskin, the example of toothed hens is not the resurrection of a lost developmental pathway but the result of an experimental mistake.

Luskin cites a paper from Marshall, Raff and Raff2 that seemingly supports his argument. In the paper, the authors devise an equation that determines the probability of a silenced gene's reversion as a function of time passed. They concluded that, for a gene that has been silenced for 10 million years, there is a near-zero probability for reactivation. How do they account for Kollar and Fisher's results? They state that "the classic example of the resurrection of "hen's teeth" is most likely an experimental artifact". Well, that settles it, right?

Well, no. Marshall, Raff and Raff's paper was published in 1994, and despite what Luskin might think, science has progressed in the two decades since. Perhaps if he had read through more recent literature he would have realized some problems with his argument and with Marshall et al's conclusion.

First, let's tackle the "experimental artifact" claim. When Kollar and Fisher's original paper was published, there was some skepticism about their results. There was controversy over whether or not the mouse mesenchyne they used was contaminated with mouse epithelial tissue. If this was the case, then their results would be invalid: it would be impossible to tell whether or not the formation of dentin was prompted by the chick epithelium or the mouse epithelium. Despite the experiment being repeated by other researchers, the possibility of contamination meant that many people wrote off their result as an "experimental artifact". This debate was put to rest, however, by an paper published by Cai et al in 20093. In their paper, the team repeated the tissue graft experiment using mesenchyne from transgenic mice expressing the LacZ gene (LacZ is used in molecular biology as a reporter gene, because it produces a dark blue pigment when supplied the proper substrate). Like Kollar and Fisher, Cai et al's results showed the induction of dentin by chick epithelium. To prove that there was no contamination by mouse epithelium, they took cross sections of the graft and stained them. The transgenic mouse tissue, expressing the LacZ gene, stained a dark blue while the chick tissue remained unstained. What they found was that the entire epidermal tissue remained unstained, while only the mesenchyne stained blue, ruling out the possibility of contamination. Kollar and Fisher's original results, then, are still valid.

So if Kollar and Fisher were correct all along, then don't their findings go against Dollo's Law? Shouldn't the genes for tooth production, being free from selective pressures, have accumulated many mutations that would prevent the pathway from functioning at all? The answer, again, is no. Perhaps if Luskin had read the Marshall et al paper more closely (if, indeed, he had read it at all, since he only quotes the abstract) he would have gotten a hint. The authors mention in their discussion that "[r]eversals of long-lost structures do occur but evidently result from the cooption of genes that continue to survive in other roles". In other words, genes involved in traits no longer expressed can avoid the fate of accumulating mutations if they have other roles in development. The genes for tooth production most certainly fit this description. Work by West et al in 19984 found that many of the genes required for odontogenesis are still expressed in the developing chick embryo, indicating that they still play important roles. BMP4, for example, plays important roles in muscle development and bone development as well as in the development of teeth. Members of the  Hedgehog family of proteins are involved in a whole slew of developmental processes, only one of which is odontogenesis. Toyosawa et al5, in 1999, looked at one protein in particular, Dentin Matrix Protein 1, or DMP1. Since birds don't produce dentin, what use would they have for such a gene? Toyosawa et al not only found that birds have this gene but found it was being expressed in the jaws of chickens. The case of hen's teeth escapes Dollo's Law because many of them are not silenced, and many of them have other functions in the developing embryo.

If you think about it, this really should come as no surprise. Dollo's Law describes what happens to single genes that control single phenotypes when they become silenced. Dollow's Law makes no claims about what happens to genes involved in complex developmental pathways. In order for Luskin to be correct, then it would require all the genes in a developmental pathway to have become silenced. Given the interconnected nature of developmental pathways, this simply is not a reality. One or two genes in the pathway may be lost, but the rest remain due to their involvement in other roles. If the missing genes are supplied, then the original, ancestral pathway is reconstructed and the ancestral phenotype is "resurrected". This is precisely what is going on in the example of hen's teeth. The tooth development pathway remains largely intact since many of the genes are involved in other roles. The genes in chick mesenchyne that respond to signals from the epithelial tissue have been lost, which is why birds do not develop teeth. But if you supply these genes in the form of mesenchyne from mice, then the lost pathway is reconstructed and teeth develop. This in no way violates Dollo's Law.

As for Dollo's Law itself, there is mounting evidence that would indicate apparent exceptions to Dollo's Law might be the rule. In the last ten years, many examples of exceptions to Dollo's Law have been noted, including the evolution of  wings in stick insects6, the larval stage in salamanders7, digit loss in some lizards8, egg laying in sand boas9, teeth in frogs10 (which, by the way, have been toothless for 200 million years, more than twice as long as birds), shell coiling in limpets11, and even the re-evolution of sexuality in Oribatid mites12. As noted by Collin and Miglietta13:
"with the growing number of phylogenetic studies showing patterns consistent with re-evolution of characters, and genetic data showing that developmental pathways can be maintained for tens of millions of years, is it time to give up Dollo’s Law? Perhaps."
So what remains of Luskin's argument but smouldering rubble? Kollar and Fisher's experimental results were not due to experimental error, their results don't violate Dollo's Law, and Dollo's Law itself is on shaky ground. Gould was perfectly correct in referring to hen's teeth as an atavism hearkening back to a bygone day of toothed birds.

Once again, an argument put forth by the ID crowd has failed. Are they incapable of delivering a good argument? It sure seems hard to find one that is the least bit compelling. You might even say they're as scarce as hen's teeth.

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1. Stephen Jay Gould . Of Hen's Teeth and Horse's Toes. 1980

2  C. Marshall, E. Raff and R. Raff . Dollo's law and the death and resurrection of genes. Proceedings of the National Academy of Sciences. 1994. 91:12283-12287

3. Cai J, Cho S-W, Ishiyama M, Mikami M, Hosoya A, Kozawa Y, Ohshima H, Jung H-S. Chick tooth induction revisited. 2009. J. Exp. Zool. (Mol. Dev.Evol.) 312B:465–472.

4. Philippa Francis-West, Raj Ladher, Amanda Barlow, Ann Graveson, Signalling interactions during facial development. 1998. Mechanisms of Development. 75(1-2):3-28, DOI: 10.1016/S0925-4773(98)00082-3.

5. Satoru Toyosawa, Akie Sato, Colm O'hUigin, Herbert Tichy and Jan Klein. Expression of the Dentin Matrix Protein 1 Gene in Birds. 1999. Journal of Molecular Evolution. 50(1), 31-38, DOI: 10.1007/s002399910004

6. Whiting MF, Bradler S, and Maxwell T. Loss and recovery of wings in stick insects. Nature. 2003 421(6920):264-7.

7. Chippindale PT, Bonett RM, Baldwin AS, and Wiens JJ. Phylogenetic evidence for a major reversal of life-history evolution in plethodontid salamanders. 2004.  Evolution. 58(12):2809-22.

8. Kohlsdorf T, Wagner GP. Evidence for the reversibility of digit loss: a phylogenetic study of limb evolution in Bachia (Gymnophthalmidae: Squamata). 2006. Evolution. 60(9):1896-912

9.V. Lynch and G. Wagner. Did egg-laying boas break Dollo's Law? Phylogenetic evidence for reversal to oviparity in sand boas. 2010. Evolution. 64(1):207-216

10.Wiens JJ. Re-evolution of lost mandibular teeth in frogs after more than 200 million years, and re-evaluating Dollo's law. 2011 . Evolution. 65(5):1283-96.  doi: 10.1111/j.1558-5646.2011.01221.x

11. Collin R, and Cipriani R. Dollo's law and the re-evolution of shell coiling. 2002. Proceedings of the National Academy of Sciences. 270(1533):2551-5

12. Domes K, Norton RA, Maraun M, and Scheu S. Reevolution of sexuality breaks Dollo's law. 2007 . PNAS . 104(17):7139-44

13. Collin R, and Miglietta MP. Reversing opinions on Dollo's Law. 2008. Trends Ecol Evol. 23(11):602-9