And the 2012 Nobel Prize in Medicine or Physiology goes to....

...Sir John B. Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent.

Gurdon's major work in this area goes back to the 1960s. In '62, in what would become a classic experiment in developmental genetics, he removed the nucleus from a Xenopus egg cell, replacing it with the mature nucleus from an intestinal cell¹.  This modified egg cell then developed into a fully normal tadpole, indicating that the intestinal cell, despite being fully differentated, still held all the necessary 'instrictions' to form an entire organism. This became one of the pioneering experiments in both developmental genetics and nuclear transplantation. Gurdon's work was perhaps most important because it challenged the then prevalent dogma that a cell's fate was set in stone once it became specialized. Gurdon showd that this was not the case.

Yamanaka's major contribution is much more recent. Yamanaka was studying embryonic stem cells, which are always in an immature, undifferentiated state. He was interested in identifying the genes which kept these cells immature, and after finding and identifying a number of them, he wondered whether these genes could be used in mature cells to induce them to revert back into pluripotent stem cells². He and his team introduced four of the identified genes into mature fibroblasts, and observed that the mature cells would revert back into stem cells. These induced pluripotent stem cells (iPSC) could then go on to differentiate into many other cell types. This was a major breakthrough, and the discovery was lauded in all corners of the scientific world.

Both these discoveries have lead to research in medicine that could change the world, and many of the potential applications have yet to be realized. The use of iPS cells in effectively treating diseases or correcting genetic disorders is just on the horizon. Both the pioneering work of Gurdon and the breakthrough work of Yamanaka are definitely worthy of the Nobel Prize, indeed!

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1. Gurdon, J. B.; Elsdale, T. R.; Fischberg, M. (1958). "Sexually Mature Individuals of Xenopus laevis from the Transplantation of Single Somatic Nuclei". Nature 182 (4627): 64–65
(Read it here!) 

2. Takahashi, K.; Yamanaka, S. (2006). "Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors". Cell 126 (4): 663

The Obligatory 2012 pre-Nobel Prize Post

It's that time of year again! The 2012 Nobel Prizes will be handed out this week. Oct. 8th will be the first, in Physiology or Medicine. Physics is on the 9th, Chemistry on the 10th. The Peace, Economics and Literature prizes are to follow but who cares about those, really?

Any predictions on the winners? You can find a list of predicted winners by David Pendleburry, who has in the past made a number of accurate predictions, here. I have no predictions myself, this year, so the winners will be a surprise for me.

As usual, I'll post the winners on my blog as they happen.

Yet Another Daily Dose of Science Journalism Fail

From the Daily Mail's website (where else) comes the following headline:

That's a pretty weighty claim. Do babies born via C-section really have lower IQs than those born naturally? What does the article go on to say?

"According to scientists, when women give birth naturally there are higher levels of a special protein in babies’ brains that helps boost intelligence levels as they develop.
Scientists at Yale University in the US say the increased levels of the protein, called UCP2, in babies born naturally could help foster their short and long term memories – key components of the human IQ – as they grow up."

 So according to the Daily Mail, babies born naturally have higher levels of UCP2 in their brains, and this means they have higher IQs. And, as is always the case, the Daily Mail has failed to cite the actual research behind their claim. So, I went ahead and found it for myself¹. What do the original authors have to say?

From their  abstract (emphasis added):

"Mitochondrial uncoupling protein 2 (UCP2) is induced by cellular stress and is involved in regulation of fuel utilization, mitochondrial bioenergetics, cell proliferation, neuroprotection and synaptogenesis in the adult brain. Here we show that natural birth in mice triggers UCP2 expression in hippocampal neurons."

And from their discussion (again, emphasis added):

"The current data suggests that the induction of Ucp2 by birth -associated physiological stress enables metabolic adaptation to a switch available nutrient utilization that is critical for proper survival and development of hippocampal and other brain neurons."

So, in other words, 1) the study was done in mice, and 2) UCP2 levels are correlated with changes in metabolism that were important for brain growth. Nowhere in the paper do the authors mention human babies and nowhere do they mention UCP2 levels having any effect on IQs. One has to wonder whether Sarah Johnson at the Daily Mail actually read the original paper.

Then again, the Daily Mail never really has been good at that science thing. They don't call it the Daily Fail for nothing.

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1. Simon-Areces J, Dietrich MO, Hermes G, Garcia-Segura LM, Arevalo M-A, et al. (2012) Ucp2 Induced by Natural Birth Regulates Neuronal Differentiation of the Hippocampus and Related Adult Behavior. PLoS ONE 7(8): e42911. doi:10.1371/journal.pone.0042911

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.

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.

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.

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

$100 worth of science fail

So the Canadian government has decided to give our bills a makeover. Gone are the days of money made out of cotton! A new era of synthetic polymer bank notes has arrived. They look pretty cool, which is good. Supposedly, these notes are harder to counterfeit, which is even better. And the $100 bill is a celebration of science, which is even more awesome. The reverse side of the bill shows a bottle of insulin, a lady working at a microscope, and a strand of DNA, as shown below.

 

 Wait a second. Something looks wrong here. Let's take a closer look...

 That helix is left-handed! DNA is a right-handed helix, not a left-handed helix. I applaud the Government for making the bill science-centric, but really, how hard would it have been to get the art accurate? The left-handed helix mistake is incredibly common, but that's really no excuse.

OM NOM NOM

From the journal Entomological Science (published online May 18th) comes this interesting predator-prey role reversal¹:

 

Yes, that is a giant water beetle eating a turtle.

The photo was snapped by Shin-ya Ohba outside of Hyogo, Japan, while collecting samples for his research. While giant water beetles are known to chow down on smaller insects and small fish, finding one dining on a baby turtle is quite bizarre. Ohba writes:

"The bug inserted his proboscis into the neck of the turtle....Although I could not confirm whether the bug caught the turtle by himself in this observation, the dead body of the turtle was fresh. Probably, he had just captured the turtle. This is a first report of a Lethocerinae eating a turtle."

Pretty neat. And also pretty scary.

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1. S. Ohba . "Field observation of predation on a turtle by a giant water bug" . 2011 . Entomological Science . doi:10.1111/j.1479-8298.2011.00450.x

This Week in Science (June 5, 2011)

Just a pair of papers for this week's TWIS. I haven't had much time to dedicate to reading new research this week, but I'll have more next week!

To start off, I'll point you in the direction of the infamous "arsenic bacteria" paper, which has finally been published in Science after languishing on Science's pre-print server for months. This paper, if you're unfamiliar with it, claimed to show the discovery of a new species of bacteria that utilized arsenic in its DNA rather than phosphorus. It was torn to shreds by critics due to problems in the authors' methodology and doubts about the results - and for good reason. Science's response to all the negative criticism that the paper has recieved has been to publish a list of criticisms (and the authors' responses) along with the paper. Jerry Coyne has a good rundown of the paper's publication on his blog.

Continuing on:

• DNA computing and square roots  - Published this week in Science is a paper by L. Qian and E. Winfree detailing an interesting advancement in DNA computing. The authors were able to design and string together DNA logic gates to create a simple molecular computer able to calculate square roots. Creating a DNA logic gate is actually quite simple, and there are multiple ways it can be done. The authors did it by using a "seesaw gate"design: the gate consists of a short stretch of DNA that can pair with multiple different sequences. One such sequence is added as an "input", which competes and replaces a second sequence that is already bound to the gate. This replaced sequence becomes the "output", which is then free to act as an input for a second gate. Gates can be strung together to create more complicated systems. The authors devised a way to string such gates together to create a system that could calculate square roots. As cool as this is, though, this early biological calculator takes a while to complete calculations - up to eight hours. Nevertheless, this is a big step towards creating bigger and more powerful DNA computers. A more detailed summary of the paper has been posted on Wired, which I highly recommend, as they do a better job explaining logic gates than me!

(L. Qian and E. Winfree . "Scaling up digital circuit computation with DNA strand displacement cascades" . Science . 2011 . 332(6034): 1196-1201, doi: 10.1126/science.1200520)

• Proteins successfully extracted from mammoth bones - A paper published this week¹ in the journal Geochimica et Cosmochimica Acta describes the successful extraction of collagen protein from 600,000 year old mammoth bones. The authors were investigating the idea that peptide mass spec. could be used to identify fossils; that is, if you could determine the sequence of proteins in the fossil, you could compare the sequences to a database of known proteins. Finding proteins which are a close match would narrow down the identity of the fossils in question. To test this idea, the authors used bones from two mammoth fossils and one mastodon fossil. After grinding samples of the fossils into powder, they performed a series of chemical extractions and washes, then prepared them for mass spec. This allowed them to sequence the extracted protein, which was confirmed as collagen. The sequence data was good enough that the collagen - and consequently, the fossils - were correctly identified as being related to elephants. The authors were even able to use this data to distinguish the samples as elephantid (mammoth) or mammutid (mastodon). These findings are important for two reasons: first, they show that proteins can successfully be recovered from fossils as old as 600,000 years; and secondly, they demonstrate that protein mass spec. can be used to correctly identify ancient fossils (or at the very least, identify the closest living relative). Exciting indeed!

(M. Buckley, N. Larkin, and M. Collins . "Mammoth and Mastodon collagen sequences; survival and utility" . Geochemica et Cosmochimica Acta . 2011 . 75(7): 2007-2016

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1. This paper actually wasn't published this week, it was published in April. For whatever reason, it looks like it only made the news now.

This Week in Science! (May 22, 2011)

This week¹ saw quite a few interesting papers in biology. Here's a few that caught my attention:

• Mammalian brain evolution driven by smell - One of the biggest characteristics that distinguish mammals from other animals is that we have relatively large brains in relation to body size. Just why mammals evolved rather large brains has been a point of speculation, but a paper published in Science this week suggests that a reliance on our sense of smell resulted in our bulging brains. The research by T. Rowe et al. involved examining the fossils of two species of Jurassic cryodonts, the group of ancient reptiles which would diverge to become the mammalian lineage. They used a technique called X-ray computed tomography to reconstruct endocasts of the cryodont brains, and compared them to those of earlier, Triassic cryodonts. They first looked at the endocast from Morganucondon oehleri, and noted that the brain was 50% larger than in earlier cryodonts. But there were other important differences: the olfactory bulbs were larger, there was expansion in the cerebral hemisphere, and the cerebellum extended to cover the midbrain. They next looked at the endocast from Hadrocodium wui, the closest known fossil to living mammals. They observed another 50% increase in brain size, with even larger cerebral hemisphere and olfactory bulbs. These observations lead the team to speculate that increased dependence on olfaction drove the evolution of larger brain sizes in early mammals. Given that early mammals were likely nocturnal, and had to rummage around in the dark for food, this idea does make sense. The researchers are now looking for evidence that might indicate that early mammals were indeed nocturnal.   

(T. Rowe et al. "Fossil evidence on origin of the Mammalian brain" 2011. Science. 332(6032): 955-957)

• Another strike against the Central Dogma - Every student in biology is brought up to know the "Central Dogma" - the idea that can be summed up as "DNA encodes RNA encodes protein". This is not a had and fast rule, though, and the discovery of things like ribozymes have shown the Central Dogma to be less dogmatic. A new paper published in Science this week furthers this point. A team of researchers lead by M. Li from the University of Pennsylvania in Philadelphia compared the DNA sequences from 27 different individuals to their corresponding RNA sequences. In a very large number of cases, they discovered that the RNA sequences that had been transcribed from the DNA sequences were different than would be expected; that is, the RNA sequences contained sites where the nucleotides had been changed. These changes in RNA sequences were shared across many of the individuals studied, indicating that the changes were not likely due to random mutation. Furthermore, using mass spectroscopy, they found peptides whose sequences reflected the RNA variant sequences rather than the original DNA sequences. What all of this suggests is that the DNA-RNA-Protein relationship is not as strict as previously thought. The DNA sequence of a gene might not dictate the exact composition of it's gene product after all. 

(M. Li et al. "Widespread RNA and DNA sequence differences in the human transcriptome". 2011. Science. doi:10.1126/science.1207018)

•  Extinction rates may be overestimated - Estimating extinction rates is an important part of ecological conservation, but unfortunately, there is really no reliable way of directly determining such rates. Instead, researchers often rely on indirect methods, but this can run into problems. One popular indirect method is to observe the number of different species found as your area of study gets larger (called a species-area accumulation curve), and then extrapolating backwards to successively smaller and smaller areas to determine the rate at which species number decreases. A new paper in Nature by Fangliang He and Stephen Hubbell argue that this method routinely overestimates extinction rates (sometimes by as much as 160%!). This comes as both good news and bad news; it means that species loss due to habitat destruction in some areas might not be as high as previously estimated, but it also means a more accurate method for estimating extinction rates needs to be devised in order to develop optimal conservation projects. 

(F. He and S. Hubbell. "Species-area relationships always overestimate extinction rates from habitat loss". 2011. Nature 473: 368-371. doi:10.1038/nature09985)

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1. Yeah, I am aware I'm posting this a little late. So sue me.

From Embryo to Adult: Body Plan Patterning in Drosophila - Part I

Take a look at a fly and it won't be long until you realize that even such a relatively simple creature is quite complex. This issue of complexity is a talking point for creationist rhetoric; "How can such complex structures just come together to create a fully formed individual?" they muse, "It must be the work of a divine creator!" Unfortunately for them, the process of development is well known and thoroughly understood. In a series of posts, I'll attempt to dispel this myth, and show just how a complex life form can arise from a single simple cell by entirely natural means. In this first part, I will introduce the concept of maternal effect genes, and one of the most important such gene, bicoid.

The development from a single egg to a full adult fly is a long one, but the process begins long before fertilization ever occurs. Consider, for a moment, the process of fertilization in humans. In humans, the egg cell is monstrous in size compared to the relatively diminutive sperm cell. There is much more cytoplasm in an egg than in sperm, and that cytoplasm is full of mRNA, mitochondria and other cytoplasmic factors. These are ultimately donated to the embryo upon fertilization: the fertilized embryo contains nuclear genetic information from both parents, but contains cytoplasmic factors from the mother alone.

Drosophila are no different. The unfertilized egg is not just a storage container for nuclear DNA, but it contains mitochondria and mRNA which will ultimately become part of the embryo after fertilization. Many of those mRNA transcripts belong to a class of genes that is very important to the development of the body plan: maternal effect genes.

Maternal effect genes get their name from the fact that they are expressed in the mother, and not in the embryo. During oogenesis, the tissues in the ovary express these genes, and the transcripts are packaged into the embryo. This is in contrast to zygotic genes, which are expressed in the nuclei of the embryo itself. One thing that makes maternal effect genes so interesting is that individual females that are mutant in such genes are phenotypically normal: the phenotype shows up in the progeny instead¹. There are about 50 maternal effect genes that play a role in the development of the Drosophila body plan, and they set up the basic framework for the zygotic genes that come later (which I will describe in a later part). Perhaps the biggest role they play, though, is in setting up the body plan axes.

The Drosophila embryo has two axes: the anterior-posterior axis, and the dorsal-ventral axis (see Figure 1). If the the adult body plan is to be laid out in the developing embryo, it is important to make sure the embryo knows which side is which (you don't want the head to end up on the wrong end, for instance), and this is the primary goal for many maternal effect genes. The first of such genes that comes into play is called bicoid, and it works to determine the anterior-posterior axis of the egg. It does this through morphogenic gradients, a concept that you'll see used extensively throughout development.

Early on in the investigation of body plan development, it was noted that those mothers who are bicoid mutants give rise to progeny without properly differentiated anterior ends (they lack a head or thorax). This fact was interesting itself, but a series of experiments made the fact all the more striking. If you take an unfertilized Drosophila egg and poke the anterior end with a needle, allowing some of the cytoplasm to leak out, they end up developing into embryos that resemble those from bicoid mutants. Furthermore, if you were to transfer cytoplasm from the anterior end of a wild-type egg to the anterior end of a bicoid mutant egg, the embryos would develop normally². It was also found that if the cytoplasm from the anterior end of a wild-type egg were transferred to the middle of a bicoid mutant egg, the embryos would develop a head right in the middle. This immediately suggested that there was some cytoplasmic factor in the anterior end of the egg that was lacking in bicoid mutant eggs, and this factor was responsible for establishing which end of the embryo became the anterior end.

If you were to look at the distribution of bicoid mRNA in the unfertilized egg, you would see just that (Figure 2). Before fertilization, bicoid mRNA is concentrated in anterior end. It remains untranslated until fertilization occurs. Upon fertilization, translation begins, and Bicoid protein diffuses through the embryo. Bicoid, then, forms a gradient, with high concentrations at the anterior end and low concentrations at the posterior end. Regions with a high concentration of Bicoid protein develop anterior structures, and the regions with a low concentration of Bicoid protein develop into posterior structures. The precise function of Bicoid will be explained in a later post, but for the moment, it is sufficient to know that bicoid activates particular zygotic genes in a concentration-dependant manner. Different zygotic genes have different threshold levels for activation, so the concentration of Bicoid across the embryo will determine which zygotic genes get activated, and in turn, determines what each region of the embryo develops into. This is the key principal behind a morphogenic gradient.

But bicoid isn't the only maternal effect gene that plays a role in setting up the anterior-posterior axis. In the next part to this series, I will discuss three more important maternal effect genes: nanos, caudal, and hunchback.

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1. If this seems confusing, remember that the genes are expressed in the mother, but the transcripts, and ultimately, the gene products, are packaged in the egg. If a maternal effect gene is mutated, the mother will be fine, but her progeny will not, because it is the eggs that are receiving the defective gene products.

2. This type of experiment is called a "rescue experiment", because it allows one to "rescue" the mutant embryos and allow them to develop normally.

From Embryo to Adult: Body Plan Patterning in Drosophila

How a fully formed organism develops from a single fertilized egg cell is a complex process. That process is no less complex in inverterbrates than in verterbrates, and much is known about just how development occurs in Drosophila. In the following series of posts, I'll detail the just how you can get a complete fly from a simple cell.

(Links will be available as I write and post each individual part)

Part I: Setting up the Anterior - Posterior Axis : Bicoid

Part II: Setting up the Anterior - Posterior Axis: Hunchback, Nanos & Caudal

Part III: The Terminators

Part IV: Setting up the Dorsal-Ventral Axis: Spätzle, Toll and Dorsal

Part V: Zygotic Gene Expression along the D-V Axis

Part VI: Gap-gene Expression

Part VII: TBD

This Week in Science! (May 13, 2011)

This week has seen the publication of quite a few interesting research articles. Here is a list of some that have piqued my interest:

• New Lizard Species Created in Lab – Many species of lizards in the genus Aspidoscelis have an interesting life history. There are a dozen species of Aspidoscelis that live in New Mexico, and about half of these species reproduce by way of parthenogenesis. Among those parthenogenic species, some have triploid genomes (that is, they have three complete sets of chromosomes), while others are diploid (two sets of chromosomes). A team of researchers lead by Peter Baumann, however, has created a new species of Aspidoscelis – one that is tetraploid. Their paper, published in the Proceedings of the National Academy of Sciences, details how they crossed females of the species Aspidoscelis exsanguis – a parthenogenic triploid species – with sexually-reproducing diploid Aspidoscelis inornata males. The matings resulted in hybrid daughters that, upon karyotyping, were found to be tetraploid. These offspring went on to reproduce asexually, giving birth to daughters that were also tetraploid. This continued for multiple generations, effectively establishing multiple lineages of a brand new species!
  (Baumann et al. "Laboratory synthesis of an independently reproducing vertebrate species". Proc. Natl. Acad. Sci.: doi/10.1073/pnas.1102811108)  

• Ribosomes Do More than Make Proteins – Every biology student is taught that ribosomes are complex ribozymes that are the "protein factories" of the cell. But new research published in Cell indicates that ribosomes are actually involved in regulating genes as well. Maria Barna's team at UCSF took a look at Ts, Tss and Rbt mice – strains of mice that all have the similar phenotypes of short, kinked tails and an extra rib. These defects mapped to the distal region of Chromosome 11, and after cloning this region in Ts mice, they found that the Rpl38 gene was deleted. Sequencing the region in Tss and Rbt mice showed similar problems in the Rpl38 gene (a frameshift mutation due to a single nucleotide deletion, resulting in a stop codon and a truncated, nonfunctional protein in the case of Tss mice; and a dinucleotide insertion at the Intron 2/Exon 3 splice site, causing a frameshift leading to a truncated protein in Rbt mice). Ribosomes are complexes of nucleic acid and proteins, and RPL38 is one such protein. It was immediately obvious that RPL38 – and by extension, the ribosome - was involved in proper development of the body plan, a process controlled by Hox genes. One question remained: how? Interestingly, when they looked at the expression of the Hox genes, the transcript levels were unchanged, so RPL38 does not provide transcriptional regulation. Rather, they found that a subset of Hox gene transcripts was not being translated by the ribosome in Rpl38 defective mice. In normal mice, RPL38 acts to facilitate the formation of the 80S ribosomal complex on these select Hox transcripts; in Rpl38 defective mice, this does not occur, the Hox genes are not translated, and the mice are born with gross physical abnormalities. Looks like ribosomes just got a little bit cooler.
  (Barna et al. "Ribosome-Mediated Specificity in Hox mRNA Translation and Vertebrate Tissue Patterning". Cell: doi/10.1016/j.cell.2011.03.028)

• Fascinating Fungi Find – Nature this week published an article about an interesting mycological find that may have implications regarding the evolution of fungi. A team of researchers at the University of Exeter in the UK began by analyzing the genomes of microbes found in a local pond. Using the sequence data obtained from these samples, they constructed a phylogenic tree by comparing the sample data with that of known species of fungi. What they found was a set of unknown sequences that was basal to the known species. They then compared these unknown sequences to those obtained from samples collected in a large variety of environments, and discovered that the fungi were almost ubiquitous. Since they appeared to be found everywhere, but had not been previously discovered, the team named the fungi cryptomycota (or 'hidden fungi'). Intrigued, they designed fluorescently labeled DNA probes that were specific to cryptomycota DNA. This allowed them to visualize which cells in the sample belonged to their newly discovered fungi. They found that cryptomycota cells were very tiny (3-5 microns in diameter) ovoid in shape. But the truly interesting part was what they lacked: a cell wall made of chitin. A chitinous cell wall is considered the defining aspect of fungal species, so cryptomycota must represent a lineage that diverged very early on in fungal evolution.
  (Jones, M. D. M. et al. "Discovery of novel intermediate forms redefines the fungal tree of life". Nature: doi:10.1038/nature09984)  

• Another Step Towards an HIV Vaccine – also published in Nature this week is a report by Picker et al on a novel SIV vaccine. SIV (simian immunodeficiency virus) is a very close relative to HIV that infects monkeys. The researchers administered the vaccine – which consisted of SIV-antigen expressing cassettes inserted into a vector made from an avirulent cytomegalovirus – to a group of 24 rhesus monkeys. 59 weeks after immunization, the monkeys were given the SIV virus. When they monitored the infection in the monkeys, they found that 13 of the 24 showed continually diminishing viral loads, and by 52 weeks, the virus was rarely detected at all. Undoubtedly, it remains to be seen if the vaccine will remain effecting in preventing SIV infection over longer spans of time, but this development is nonetheless a groundbreaking step towards an effective vaccine for HIV.
  
  (Picker et al. "Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine". Nature: doi:10.1038/nature10003)
  

Sex Determination and Lizards

Sex determination is a pretty hot topic in molecular biology. Trying to elucidate the underlying mechanisms that determine whether a fetus is male or female has been a productive field. Many species rely on a hemizygous¹ method of sex determination, and we humans are no exception (but rather, we are the rule). Males are XY and females are XX, and this is the way it works in all mammals² (even in monotremes like the platypus, though monotremes go to the extreme and can have as many as ten sex chromosomes; a male platypus is XYXYXYXYXY, for instance). Birds rely on a similar ZW system, but in this case, the females are heterogametic; females are ZW and males are ZZ. Some insects use an entirely different system, the XO system, where there is only one sex chromosome - X - and females have two (XX) whereas makes only have one (XO)³.

Despite the system used to determine sex, all the above examples have something in common: they all rely on genotypic sex determination (GSD). In these cases, it is the sex chromosomes (the number, presence or absence) which determines the sex of the resulting fetus. GSD, however, is not the only mode of sex determination. External environmental factors may also influence sex determination. Crocodiles, for example, have no sex chromosomes whatsoever. It is the temperature of the eggs which determines the sex; eggs laid in a warm nest become male and those in a cooler nest become female. Environmental sex determination (ESD) and GSD are not mutually exclusive, of course, and it has been known that many species of reptiles rely on both GSD and ESD. The interaction between ESD and GSD in these species was not thought to be a complex one; eggs at moderate temperatures use GSD, but the sex-chromosome method is bypassed and a temperature-dependant method is used if the eggs are at more extreme temperatures.

A new paper in Current Biology, however, shows that things might not be so simple.

Rajkumar S. Radder, David A. Pike, Alexander E. Quinn, and Richard Shine looked at sex determination in the eggs of the lizard Bassiana duperreyi⁴. They were examining how temperature effected the sex of the hatchlings when they noticed a correlation between the size of the eggs and the resulting sex: those eggs that were larger had female hatchlings and the smaller eggs had male offspring.

Of course, a simple correlation like this does little to prove an actual relationship and may simply be coincidence. So Shine and colleagues decided to try adding or removing yolk from the eggs during their development. What they found was pretty astounding. When they added extra yolk to the eggs, the hatchlings came out female, even if the sex chromosomes had already determined the sex to be male. And those eggs that had yolk removed switched to male even when the sex chromosomes had been set to female. This finding would suggest that sex determination in B. duperreyi is determined by a complex interaction of a minimum of three factors: sex chromosomes, temperature and egg size.

This also suggests that sex determination in any species may not be as simple as once thought.

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1. Hemizygous may not be a term you learned in Genetics 101. Whereas homozygous and heterozygous refer to having one or two different alleles, respectively, hemizygous refers to having only one of a set of two chromosomes. Female humans have two X chromosomes (XX), whereas males are XY; they are hemizygous with respect to the X chromosome. You could also refer to females as homogametic and males as heterogametic.

2. To be more specific, sex determination in mammals relies on a gene called sry (Sex-determining Region Y) located on the Y-chromosome. The gene encodes for a transcription factor called TDF (testis determining factor). When TDF is expressed, it influences the undeveloped gonad to develop into testes instead of the default state of developing into ovaries. If the SRY region of the Y chromosome is deleted or mutated, then the resulting child will be phenotypically female but genotypically male. Likewise, a translocation of SRY onto an X chromosome can lead to children who are phenotypically male but genotypically female. Interestingly, TDF does not begin to work, and consequently sex is not determined, until after the nipples have developed, which is why men have nipples that are pointless (beyond giving purple nurples, of course).

3. One interesting downside of this system is that it can lead to bilateral hermaphroditism. It is possible for the X chromosome to form a "ring chromosome" where the ends of the chromosome fuse together to make a ring. This ring chromosome is easily lost during cell division. If an embryo begins as XX (female), and very early on in development (at the 4 cell stage, say) a ring chromosome is formed and lost in one cell, the embryo will become split right down the middle, one side being male and the other side being female. This is rare, but not uncommon, in Drosophlia. Such flies are called gynandromorphs.

4. Rajkumar S. Radder, David A. Pike, Alexander E. Quinn, and Richard Shine. Offspring Sex in a Lizard Depends on Egg Size. Current Biology, 2009; DOI: 10.1016/j.cub.2009.05.027

On Assumptions and Conclusions

One of the things that creationists often say that really annoys me is that evolution and creationism are not all that different in that they both rely on the same facts and observations, but come to different conclusions because they use different starting assumptions. Biologists, they claim, begin with the assumption that natural selection, common descent and descent with modification are all real phenomena, while creationists begin with the assumption that the Bible is the inerrant word of God. They posit that, because the two groups use different starting assumptions, they interpret the data differently, in a way which confirms their preconceived views; when a biologist looks at a giraffe, she sees the byproduct of billions of years of evolution, whereas a creationist sees obvious design.

This claim is absolute rubbish. Anyone who makes such a claim is exposing their incredible ignorance of the scientific method. In fact, such statements run completely contrary to the way the scientific method is supposed to work!

Generally, the scientific method works like this: you gather observations and empirical data, and from analysing the observations and data, you draw out general conclusions which explain all of the data. In other words, science does not start with any unfounded assumptions; it begins with the data, and from the data determines general principals on how the world works. Scientists do not begin by assuming the nonexistance of God - God doesn't even factor into the equation for the most part. In the case of evolution, biologists do not begin with assuming God does not exist and then interpret the data in a secular manner; instead, biologists determine from the data that species arise from a purely naturalistic process, and God's non-involvement follows as a natural conclusion.

Creationists, on the other hand, follow such counter-scientific principals to the tee. They start with their supposed conclusions - goddidit - and then ask "What facts can we find that support our conclusion?" To creationists, facts follow conclusions and not the other way around. They begin by assuming that the Bible is the inerrant word of a supernatural entity, and then stretch, skew and distort any facts they find to try and make them fit into their biblical beliefs.

The idea that science and religion simply begin by making different starting assumptions is antithetical to science. This is a big part of the reason why "creation science" is such a huge joke.