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.

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!

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

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.

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)
  

Nephy's Nylonase Nonsense

Oh, Nephilimfree, you've done it again. You went and dragged genetics through the mud again, and I won't stand for it.

At this point, having dedicated a few posts to his inane ramblings, debunking Nephy's claims is beginning to feel like picking on the fat kid at the playground. He's a slow, lumbering target, and all the other kids on the playground keep picking on him because he's easy prey. But Nephy is so ripe with nonsense, so overflowing with vacuous crap like a bountiful cornucopia of bullshit, that it's hard to resist tearing his arguments apart when I'm looking for something to write about. And his silly website [Edit: 06/11/11: Looks like Nephy has let his registration of his domain lapse, so that link doesn't work any more. I tried to find an archived version, but had no luck] has no shortage of fodder for a creationist asskicking.

This week, I took a look at this article he wrote about the enzyme nylonase. You've probably heard about nylonase before, as it is often given as a great example of an evolutionary adaptation that has occurred in recent history. In 1975, a team of researchers from Osaka University in Japan got the idea to try and culture sludge obtained from the waste water outside of nylon factories¹. The samples they collected were used as inocula, and added to cultures which contained a form of nylon (6-aminohexanoic acid cyclic dimer) as the sole carbon and nitrogen source. Any bacteria that grew would have to rely on metabolizing nylon to survive. And grow they did. They designated the strain as KI72, and after isolating the bacteria, they identified it as a strain of Achromobacter guttatus, although later work by the same team reclassified the species as a strain of Flavobacterium². A few years later, the researchers identified two novel enzymes which allow the bacterium to metabolize nylon: 6-aminohexanoic acid cyclic dimer hydrolase and 6-aminohexanoixc linear oligomer hydrolase (6-AHA CDH and 6-AHA LOH, respectively)^3,4. Since nylon production began in the 1930s, these enzymes had to have originated in the time since then. After all, it doesn't make much sense for a bacterium to  have produced enzymes to specifically degrade nylon before nylon itself was invented. These genes, then, represent an example of a novel adaptation arising outside of the lab and within the past century.

But Nephy disagrees. He states, 

"Because the bacteria encountered nylon and developed an ability to digest it does not provide evidence of any kind of evolutionary change. This ability does not effect the form and structure (morphology) of the bacteria by introducing any new structural feature, nor does it transform any existing structural feature of the bacteria into a new kind of structure with a new physiological function."

Two paragraphs in, and he's already run into a major problem. He seems to have this odd idea that unless a change results in gross morphological alterations, it cannot be an evolutionary change. He simply discredits novel biochemical adaptation out of hand without any sort of justification. He simply wishes to define evolution as changes in "form and structure" and ONLY changes in "form and structure" - any other kind of change he refuses to acknowledge as evolutionary change. In essence, he's defining evolution in his own incredibly narrow terms, so that any actual evolutionary change can be shrugged off as "not evolution". If we were to narrowly define creationism as "the spontaneous formation of aardvarks from forest detritus", it would be pretty easy to discredit, too.

But beyond that, it is simply silly to only accept large changes in morphology as the only kind of evolutionary change. Morphological alterations cannot occur all at once. Any modification to an organism's body plan would require many not-so-obvious biochemical changes to occur first - the very type of changes that Nephy does not accept as "evolution". Evolution can only work with what it has available. No organism is going to mutate and grow wings de novo all in one shot, even if it would be advantageous. Such changes would require modifying the existing body plan, and this would require extensive biochemical changes to happen first.

Nevertheless, the discovery of novel nylon-degrading enzymes is indisputable. Musing over the origins of these enzymes, Nephy declares that these proteins, or any protein, could not have simply evolved. No, he says, statistical analysis says otherwise:

"The field of sicence [sic] called Statistical Ananlysis [sic] which is employed to determine probability in various fields of science, has determined that the formation of proteins by random molecular interactions is on the order of 10^950, which is 1 to a number for which no name exists; a number greater than all of the paticles [sic] of matter in the speculated universe. In other words, according to science itself, the chance of a single, medium-sized protien [sic] arising by purely materialistic molecular interactions is considered impossible to science because it is considered impossible times impossible times impossible. The evolutionist would have you believe that random mutation is capable of producing novel protiens [sic] which have specific function, but this is not only unfounded but exceedingly irrational."

This is a typical creationist talking point: whipping out statistics to churn out large numbers and proclaim "See! It's statistically impossible for evolution to occur!"  It is also typical, as Nephy demonstrates quite well, for creationists not to cite the source of these statistical calculations. The problem with Nephy's argument is that he does not take into account the process of selection during evolution. Forming a protein "randomly" and all at once is incredibly unlikely (though not entirely impossible), but if you factor selection into the equation, it becomes an incredibly likely phenomenon. Richard Dawkins illustrates this beautifully in his book The Blind Watchmaker, where he likens evolution to monkeys banging away at typewriters. If you were to wait for a monkey to type out the sentence "Methinks it is like a weasel", you'd be waiting for eons for it to "randomly" happen. But suppose you were to use cumulative selection to pick and keep the letters that work. Dawkins wrote a computer program to do just this (as computer programs are much cheaper and easier to work with than hordes of monkeys). Starting with a string of gibberish and then changing one letter per generation, the computer program "evolved" the correct sentence is about 40 generations⁵. It took only a few minutes for the computer program to complete this task, whereas single-step selection (waiting for the correct sentence to happen randomly, and all at once) would have taken the computer "a million million million million million years"⁶. Obviously, selection gets past the staggering statistical improbability that creationists argue.

But Nephy continues. He tells us that it was discovered that the nylonase genes originated from a frameshift mutation, resulting in an alternate reading frame which produced a novel enzyme⁷. This may be true, but recent work by Negoro et al indicates that the origin of the genes might be due to base substitutions after an ancestral gene duplication⁸. Nephy proceeds to tell us that there are only two ways that such a frameshift can occur: a random mutation or by a "Programmed Translational Frameshift Mutation".

At last, we come to the crux of Nehpy's argument. According to him, random frameshift mutations are invariably bad and the idea of a random frameshift mutation is a cop-out employed by "evolutionists" to ignore the reality of intelligent design. The origin of nylonase must be due to "Programmed Translational Frameshift Mutation", a process, he claims, is divinely inspired..

At this point I feel I should clear something up. Nephy, I hope you're reading. There is no such thing as "Programmed Translational Frameshift Mutation". Programmed Translational Frameshift (PTF) is a very real process, but it is not a mutation. PTF actually describes a variety of complex, but similar, processes. The essence of the idea is this: under normal circumstances, a protein is produced when a ribosome translates a strand of mRNA. Usually, the ribosome translates in a linear fashion, starting at the 5' end of the strand and reading the length of the strand until it comes to a stop codon at the 3' end. But in certain cases, the ribosome can be induced to "skip" or "hop" over a number of nucleotides in the sequence. The result is that the ribosome is shifted out of frame, and the resulting gene product is unlike the original⁹. With PTF, one gene sequence can produce multiple gene products: the original, unshifted, product and the second, shifted, gene product. This process is not a mutation. Mutations are changes to the genetic sequence itself, and such changes do not occur during PTF.

Perhaps Nephy's mistake stems from him being unable to comprehend the scientific literature. In his article, he describes PTF as "the modification of the arrangement of amino acids in a chain caused by information in the DNA which programs the event to occur", which is inaccurate, to say the least. This is further evidenced by the fact that he chooses to illustrate PTF with a diagram of alternative splicing, which is an entirely different process altogether! These errors would indicate that he simply did not understand what PTF is. I get the feeling that Nephy just skims through paper abstracts, pulling out words to form misshapen ideas, rather than taking the time to actually read any scientific papers.

But, regardless of whether or not PTF counts as mutation, Nephy's argument that nylonase originated due to PTF, rather than a simple frameshift mutation, doesn't hold much water. What we know about nylonase - the gene's sequence, how it is regulated, etc - would indicate that PTF is NOT at play here. As mentioned above, PTF occurs when a single transcript is read in two different reading frames, resulting in two different gene products. But in the case of nylonase, there is only ONE reading frame. It is always read by the ribosome in the same fashion. At no point is the ribosome prompted to switch to a new reading frame during translation - a hallmark of PTF. In many cases, this switch is induced by particular sequence elements, but the nylonase gene does not contain any such sequence elements. All evidence points to an ancestral gene that underwent a frameshift mutation that permanently altered it's reading frame, rather than two different and active reading frames from a single sequence. The original frameshift alteration was likely transcriptional in nature rather than translational.

Nephy's claim that random frameshift mutations are always harmful is nonsense as well.  In any case where a mutation is deleterious, creationists are quick to say "See! Random mutations are bad!"; any case where a mutation proves to be beneficial, they shout "That didn't count! That was Intelligent Design!". This amounts to little more than special pleading. Nephy does not see it this way. He states 

"The problem for evolutionists is that we have discovered that random frameshift mutations produce novel proteins which do not have a function in the cell, and when produced in great numbers, are causes of diseases such as Alzheimers and Tay-Sachs."

But how are deleterious mutations and non-functional proteins a problem for evolution? On the contrary, they are a huge problem for Creationists! After all, why would God allow for non-functional proteins to cause deadly conditions? Why would God allow for mutations to begin with? Pretty sloppy work for a Creator who is supposedly "perfect".

Another issue with his argument is how he ascribes PTF as an "intelligent design process". What evidence does he have that PTF is not a naturally occurring process? Why does he call it intelligent design? He gives no reason. He simply slaps the ID label on and announces "Hah! PTF proves intelligent design!" with no justification whatsoever. One could just as easily label espresso brewing "intelligent design" and proclaim that Starbucks baristas are evidence of divine creation. It is nonsensical. 

Nephy proceeds with a few paragraphs of rambling spew about DNA being a "computer code". I have already talked at length about why DNA is not a code, so I will not go into it here. Needless to say, it makes little sense.

So what it all comes down to is this: the nylonase gene is a product of a frameshift mutation and not programmed translational frameshift; programmed translational frameshift is not a mutation, nor is it evidence of Intelligent Design; biochemical adaptations do count as evolution; and nylonase still illustrates a wonderful example of evolution occurring within recent memory.  Once again, Nephilimfree abuses genetics to form a murky mire of distorted truth, and once again, his claims do not stand up to the scrutiny of critical thought.

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1. Kinoshita, S.; Kageyama, S., Iba, K., Yamada, Y. and Okada, H. (1975). "Utilization of a cyclic dimer and linear oligomers of e-aminocaproic acid by Achromobacter guttatus". Agricultural & Biological Chemistry 39(6): 1219−23

2. Negoro, S.; Shinagawa, H.; Nakata, A.; Kinoshita, s.; Hatozaki, T. and Okada, H. (1980). "Plasmid control of 6-aminohexanoic acid cyclic dimer degradation enzymes of Flavobacterium sp. KI72".  Journal of Bacteriology 43(1): 238-245

3. Kinoshita, S.; Negoro, S.; Murayama, M.; Bisaria, V. S.; Sawada, S. amd Okada, H. (1977). "6-aminohexanoic acid cyclic dimer hydrolase . A new cyclic amide hydrolase produced by Achronobacter guttatus KI72" European Journal of Biochemistry. 80: 489-495.

4.  Kinoshita, S.; Terada, T.; Taniguchi, T.; Takene, Y.; Masuda, S.; Matsunaga, N. and Okada, H. (1981). "Purification and characterization of 6-aminohexanoic-acid-oligimer hydrolase of Flavobacterium sp. KI72". European Journal of Biochemistry. 116(3): 547-551

5. Dawkins, R. (1986). The Blind Watchmaker, p. 48

6. Ibid. p. 49

7. Ohno, S. (1984). "Birth of a unique enzyme from an alternate reading frame of the preexisted, internally repititious coding sequence".  Proceedings of the National Academy of Sciences. 81: 2421-2425

8. Negoro, S.; Ohki, T.; Shibata, N.; Sasa, K.; Hayashi, H.; Nakano, H.; Yasuhira, K.; Kato, D; Takeo, M. and Higuchi, Y. (2007). "Nylon-oligomer degrading enzyme/substrate complex: catalytic mechanism of 6-aminohexanoate-dimer hydrolase". Journal of Molecular Biology. 370: 142-156

9. Farabaugh, P. (1996) "Programmed Translational Frameshifting". Microbiological Reviews. 60(1): 103-134 

Another creationist doesn't understand science. Who knew?!

Nephilimfree, Youtube creationist extraordinaire and posterboy for the giant headphone lobby, has posted a new video entitled "Overlapping and Embedded Genes". Unfortunately for him, I am a lover of any and all things genetic. Also unfortunately for him, he doesn't have a clue what he's talking about. Fortunately for me, this provides me an opportunity to tear his video to shreds.

A little background may be necessary. Nephilimfree (who I will henceforth refer to as "Nephy", as I am an avid believer of making infuriatingly inane things tolerable by giving them cute names) made this video in response to a conversation he had with Sofiarune. He does not mention it, but I was also involved, as I am Sofiarune's go-to guy for molecular biology. I guess you can say I have a personal interest in this video, but I'd pick apart Nephy's claims in any event since they are, as usual, stupid on a Goats On Fire level.

First, the video. Be warned, it is rather long, running at just over 14 minutes. If you don't have the time (or the patience) to watch the whole thing, I'll give you the tl;dr (...or is that tl;dw...) version below. Go grab some coffee, because this post is gonna be a long one.



Nephy's argument is basically this: (i) the existence of overlapping genes is an obstacle to evolution because a single mutation will be deleterious to multiple genes and (ii) these gene pairs could not have possibly evolved and are thus evidence that they have been created. As we will see below, both of these points are patently false, and they demonstrate the extent to which Nephy is ignorant of both evolution and genetics.

Nephy starts the video off by mentioning his discussion with Sofiarune, and his insistence that genes overlap and that this is somehow proof that evolution isn't true. He states that "being the evolutionist that she is, she said 'No, no, no. Genes are read linear and they are not embedded'." Nephy is only telling a half truth here. In their original conversation, he presented "overlapping genes" in a very different manner than he does in this video, as the figure below demonstrates:

 

So Nephy broached the subject with a cryptic sentence about overlapping sequences "causing entropy" to "the code". Understandably, Sofia asked for clarification. In response, he talked about overlapping sequences in shotgun sequencing. This is entirely different. Overlapping sequences in shotgun sequencing and overlapping genes in the genome are not the same thing - one is a bioinformatic technique used to align sequence data in the proper order and the other is the idea that sequences can have multiple open reading frames (ORFs) coding for different gene products. He followed this up with a link to an article [not shown] which further obfuscated what he had meant. It talked about how, in the early days of molecular biology, there was debate over how the genetic code was read; were sequences read in one long linear manner, or were all three possible reading frames of a sequence read at once, resulting in overlapping sequences? It was determined early on that the correct answer was the former - codons were read one at a time in a linear fashion. In this context, Sofia was entirely justified in saying that genes did not overlap. Nephy seemed to have gotten all these concepts confused, but in his video, he presents it as if he gave Sofia a concrete definition of "overlapping genes". Leave it to a creationist to be vague, only to misrepresent your response.

Nevertheless, Nephy now has a concrete definition: overlapping genes are multiple coding ORFs contained within a sequence. Such overlapping genes do exist, primarily in RNA viruses. A study done by Chirico et al¹ (which I will go into some detail below) found that 75%  of the 2000 or so known species of virus have some extent of gene overlap. This does not mean that it is a widespread phenomenon as Nephy seems to believe. He points to an article entitled Mammalian Overlapping Genes: The Comparative Perspective² and is seemingly impressed by the numbers. It shows a total of 774 total overlapping genes in the human genome, and this might be impressive to Nephy, but it isn't to anyone who actually took the time to read the paper. This 774 is out of the 34,604 annotated gene sequences posted to the NCBI human genome assembly (build 33). That's a whopping 2.2% of genes.  So overlapping genes in humans are more the exception than they are the rule. This is the same for pretty much all eukaryotic organisms; overlapping gene sequences do exist, but they are pretty rare. They are mostly seen in viruses (indeed, overlapping sequences were first discovered in he late 1970s by researchers working with the phage φX174). Nephy talks about overlapping genes as if they are as numerous as the grains of sand on the beach, but they are actually quite infrequent. 

But Nephy isn't only concerned with the existence of overlapping genes. He claims that overlapping genes are a problem to evolutionists. He thinks this is because a mutation in the overlapping sequence would be deleterious to both genes and evolution could never favour such a situation. This is demonstrably false, and the evolution of overlapping genetic sequences can, and has, been explained. A paper by Rancurel et al.³ (2009) did just that. According to the authors, there are two characteristics of overlapping genes that alleviate evolutionary constraints on them: (i) overlapping proteins are full of amino acids with a high level of codon degeneracy and (ii) the regions of proteins encoded by overlapping sequences have a tendency towards structural disorder. It is worth going into some detail about these.

(i) To understand what the first point means, you will need to understand what is meant by "codon degeneracy". There are 64 different codons which can be constructed from the four nucleotides, but only 20 main amino acids which comprise any polypeptide. This means that there will be some amino acids that are encoded by multiple codons. Arginine, for example, has 6 different codons - CGU, CGC, CGA, CGG, AGA, and AGG. You'll notice that these codons are pretty similar to each other, and that is pretty handy for the cell. If, for instance, a mutation changes a CGU codon into CGC, CGG or CGA, it will still encode for arginine. The sequence has changed, but the output of the sequence remains the same. The mutation will have no effect on the protein sequence. This is what is meant by codon degeneracy. Amino acids with codon degeneracy will be able to tolerate some degree of mutation. This is important to overlapping genes, because the proteins produced by overlapping genes are high in amino acids that have codon degeneracy. What this means is that mutations to the sequence can be tolerated and won't have a deleterious effect. This is quite the opposite of what Nephy claims. He feels that a mutation will be doubly deleterious to overlapping genes, and he would be right if it weren't for the high frequency of codon degeneracy found in these proteins. In many cases, a mutation will have no effect at all on either protein in the pair.

ii) Structural disorder describes the extent to which the 3D structure of a protein is defined. Those proteins with a high degree of order have a strictly defined 3D secondary structure, while those with a high degree of structural disorder do not. They tend to rapidly change from one structural form to another - their secondary structure is not strictly defined. Since it is the amino acid sequence of a polypeptide that largely determines it's 3D shape and thus function, those with a high degree of structural disorder can tolerate some degree of mutation. Mutations will not affect the protein's 3D shape much because it doesn't have a definite shape to begin with. As the authors put it, "[d]isordered proteins are generally subject to less structural constraint than ordered ones". It should not be surprising, then, that the regions of proteins which are encoded by overlapping sequences tend to be structurally disordered. Those parts do not have a rigid secondary structure, so mutations will have less of a deleterious effect on these overlapping regions. Again, this is antithetical to Nephy's claim that mutations in overlapping genes are a death sentence for a cell.

As an aside, this point about structural disorder raises an interesting theological question: if overlapping genes were created by God as Nephy believes, then why did God decide to create proteins which have regions of structural disorder? If he created these proteins for a particular reason, then would he not have designed them all to have a definite 3D structure that belies their function? Did God just get lazy and figure "Eh, I'll just make some of these proteins structurally ambiguous. No one's gonna notice"? From a design perspective, it doesn't make sense, especially when the designer is perfect and all powerful. Why would he even design overlapping genes to begin with? Wouldn't he just stick to the good old "one gene = one gene product" plan? It's much simpler. It's a hallmark of poor design when things are more complicated than they need to be. How can a perfect God have an imperfect design, anyway?

So Rancurel and co. have thoroughly shown Nephy's point on mutation to be bunk. But they also give his claim that overlapping genes could not have evolved a thrashing. In fact, they do this in the very first paragraph of their paper! They state:

"Among several mechanisms, they [overlapping gene pairs] can be created by a process called "overprinting", in which a DNA sequence originally coding only one protein undergoes a genetic modification leading to the expression of a second reading frame in addition to the first one...The resulting overlap encodes and ancestral "overprinted" protein region and a protein region created de novo (i.e., not by duplication) called an "overprinting" or "novel" region" [See figure below, click to embiggen].

In other words, overlapping gene pairs can be explained easily by a natural process. Two genes exist with reading frames shifted relative to one another, with one upstream from the other. The loss of a stop codon in the upstream gene results in this gene being extended into the region of the second gene where it ends at a stop codon. The result, then, is two genes which share a region of sequence. This has an important evolutionary consequence. The novel region is free to take on novel cellular functions. For the reasons stated above, the novel region is under fewer constraints. In fact, the creation of proteins de novo in this manner has likely played a very important part in viral evolution⁴. In many viruses, the novel protein in overlapping protein pairs are virulence factors or encode enzymes that allow the virus to escape host defence mechanisms. De novo creation of novel proteins by overlapping genes represents another mechanism by which novel "information" is added to the genome, something creationists love to deny is possible. 

But not only can we explain how overlapping proteins pairs have evolved but we also have some good ideas why they would evolve. Chirico et al give four possible reasons why overlapping gene sequences may have evolved in viruses.

1.  Mutation rates: given the high mutation rates seen in viruses, it makes sense that there is pressure on viruses to keep their genomes short. Longer genomes will accrue more mutations than shorter ones. Overlapping genes are a way for a virus to expand its repertoire of genes without extending its genome.
2. Capsid size: some viruses have capsids of limited size. Increasing the size of these capsids to accommodate increased genome sizes is quite the undertaking and is likely to have a fitness cost. Thus it would be advantageous for the virus to have genes which overlap, since this takes up less space within the capsid. 
3. Gene length: larger genomes tend to have less overlap than smaller genomes. This might be because there is more room in larger genomes for the genes. Viruses may have overlapping genes simply because they have small genomes and cannot fit all the genes linearly.
4. Expression regulation: it is possible that overlapping genes evolved so that the genes in a gene pair can be regulated together.

The authors studied the sequence data from 62 different virus families to see which of the four possibilities best matched. They determined the likely cause for the evolution of overlapping genes in viruses was the constraint caused by capsid size. Nonetheless, it is entirely possible that any of the other three may have occurred in certain cases.

The reason I bring this up is because science has at least made an attempt to explain why overlapping genes exist at all. Nephy and his creationist brethren are content to claim that God created overlapping genes but they don't say a word about why he would have done so. The naturalistic explanation offered by evolution not only explains how but also why. The explanatory power of evolution is massive, while creationism offers little more than just-so stories and ad hoc justifications.

But despite all this, Nephy talks for 9 minutes about how overlapping genes are evolutionarily impossible, while saying absurd things like "Geneticists today are shying away from the use of the word 'gene' because it really doesn't describe what we observe in the genome of life. The preferred term is 'sequences' because it is difficult to say what code ends where and starts where in some cases". As someone with a degree in molecular genetics, this took me by surprise. No one sent me that memo! This statement makes little sense; genes and sequences are not equivalent, and it's actually pretty easy to determine where one sequence starts and one sequence ends. We've even been able to develop computer software that can predict such things in a matter of milliseconds. Given that Nephy has little scientific background and is definitely not part of the geneticist community, I'd like to know just where he got the idea that the term "gene" was passé. It's still very much a useful term and is used constantly in the scientific literature. 

He finishes off his video with a five minute snippet of a talk given by Hubert Yockey. I find it amusing that Nephy introduces this clip by saying "And now a few select moments from a lecture by a geneticist", followed immediately by a screen declaring "Biophysicist Hubert Yockey". Nephy, a biophysicist and a geneticist are not the same thing. Not even close. And Yockey isn't even a biophysicist to begin with; he's a physicist. He did some work on information theory and how it applies to biology, but this does not make him a biophysicist. I know these are big words for you, but do try to understand the distinction between them before you toss them around again. I won't actually go through the claims made by Yockey in the video (to be honest, I didn't even watch that part) because really, a physicist's claims about biology are about as meaningful as a butcher's claims about nuclear physics.

So once again, Nephilimfree has demonstrated that he has no idea what he is talking about. Overlapping gene sequences are NOT evidence of Divine creation - they make no sense if one assumes they were created, and they make perfect sense when interpreted in the light of evolution. We have a perfectly naturalistic explanation of their origin which conforms to experimental observation. Furthermore, mutations within overlapping genes are not always a bad thing, and have likely contributed to the evolution of pathogenicity in many species of virus. His claim that mutations in overlapping genes are always deleterious is patently nonsense. In fact, at one point in the video he claims that "all genetic mutations cause degretory[sic] effects to the genome's code", a claim that literally thousands of examples can disprove. He says that he has told evolutionists this for a long time and they "refuse to listen". There's a simple reason for that, Nephy - it's because you're flat out wrong.

Consider this a challenge, Nephy. Show me how what I have written is incorrect. Show me why the authors I have quoted are wrong - critique their work. Give me evidence taken from peer-reviewed scientific literature that backs up your claims, and not just idle speculation on your part. Give me a thorough refutation, thoroughly sourced. Because until you do your claims will be little more than verbal diarrhea.

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1. Nicola Chirico, Alberto Vianelli and Robert Belshaw. Why genes overlap in viruses. Proceedings of The Royal Society Biological Sciences . 2010 . 277: 3809-3817

2. Vamsi Veeramachaneni et al. Mammalian overlapping genes: the comperative perspective . Genome Research . 2004 . 14:280-286

3. Corinne Rancurel et al. Overlapping genes produce proteins with unusual sequence properties and offer insight into de novo protein creation . Journal of Virology . 2009 . 83(20): 10719-10736

4. F. Li and S. W. Ding . Virus counterdefence: diverse strageties for evading the RNA-silencing immunity. 2006 . Annual Review of Microbiology . 60:503-531

Theistic Evolution, a Case of Special Pleading and a Case of Denying Evidence

Not much in the way of science in this post, just something I had been musing about for a while.

Among people of the religious persuasion, there seem to be three main camps of people when it comes to attitudes towards evolution. There are those who outright deny evolution is possible - the Ken Hams and Ray Comforts of the world - and a large chunk of time is often dedicated to debunking the asinine claims of these nutjobs. There are those creationists who will accept "microevolution" but deny "macroevolution" (whatever such a distinction means, if anything) - individuals who will accept what they see as "just" adaptation within populations but are still diehard creationists at heart. And then there are the "theistic evolutionists" - people who will accept that evolution is completely true but nonetheless insist that life was originally started by God; they posit that God acted as a sort of kickstart for evolution. In a sense, they are still a form of creationist, albeit a "weak creationist", since they still believe that life was created by a supernatural force and evolution proceeded from there. But there is another form of creationist, one that falls in between the last two categories. These are the individuals who will accept evolution in all cases except as it applies to humans. They believe humans to be God's "chosen" species (though, given the plethora of ailments we humans often suffer from, one might begin to wonder what benefit being chosen has, if any), and we were created in cutis by God as mentioned in the Bible and have remained the same ever since. This is a weaker form of theistic evolution (which itself is a weak form of creationism¹!), and quite obviously, a case of special pleading.

All of these positions are untenable for a variety of reasons but it is the problems with this last position - that of the "evolution for all but humans" proponents (which I'll refer to as Humans-Only Creationism, or HOC, for simplification) - that I wish to focus on.

Being that those who hold such a view are accepting of the evidence for evolution in all cases except that pertaining to the evolutionary history of hominids, it is perhaps unexpected that evolutionary evidence of the hominid lineage would raise issues for this view point. Let us assume for a moment that humans are a special case - that they were created as is by God, and have remained unchanged since their genesis. What, then, would we make of the other hominid fossils that have been found? Since HOC makes the claim that humans have not evolved, then these fossils could only possibly be either fully "human" or fully "non-human" (or "fully ape", most creationists would claim), as any gradient between the two would indicate evolution. But this is problematic. Firstly, how would one determine which category any particular fossil specimen belonged to? Many fossils have traits that are "human-like" and also other traits that may be described as "ape-like". No one specimen has characteristics of only one or the other - they are an amalgamation of traits both human- and ape-like. Secondly, the record of hominid fossils does show a gradient from more "ape-like" to more "human-like" in many characteristics, and to claim that such a gradient does not exist is to outright deny observable fact.

Also, the "ape-like" hominids create problems for HOC. If they are not hominids, then what, exactly, are they? They are obviously more like humans than any extant primate. Are they supposed to be Gods "failed attempts" at creating humans? But if God is supposedly omnipotent, then how could this be? How could a perfect being create an imperfect creation? He would surely have gotten it correct on the first attempt. Anyone who subscribes to HOC has no choice to claim that God created them for a specific purpose. Why, then, did he create them so similar to humans?

HOC proponents are also guilty of doublethink. They freely admit to accepting evolution for all other species based on the overwhelming evidence in its favour. But in the same breath, they dismiss with a wave of the hand the idea that humans evolved - an idea which is based on the very same sort of evidence that they accept for other species! How one can hold these two beliefs at once and not succumb to crippling cognitive dissonance is beyond me.

When the evidence is examined, of course, the reality shows though - humans, like every other animal in existence, is the product of countless years of evolution.
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1) Perhaps we should call this idea "doubleweak creationism".