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)
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.
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.
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)
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)
"According to mainstream scientists and chronologists, based on uranium-lead series radiometric dating of moon rocks the Earth is only 4.6 billion years old therefore years did not exist before that because the Earth wasn't orbiting the Sun." [emphasis added]
I really wish I had a witty retort here, but I'm dumbstruck at the sheer ignorance.
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.
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.
---------------------------------------------------------------------------------- 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 Chemistry39(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 Bacteriology43(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
This isn't going to be a long, lengthy post, but rather a short note on an interesting paper just published in Frontiers in Systems Neuroscience, detailing a neat advancement in ultramicroscopy.
As you probably already know, Drosophila is perhaps the most commonly used model organism in genetics. When a geneticist used Drosophila for a genetic screen, he generates mutants and then scans the progeny for particular desired phenotypes. For instance, if you're interested in a gene involved in the development of limbs, you'd generate mutants and then look for ones that have mutated legs. External phenotypes like this are pretty easy to observe, even without a microscope, but it's a bit harder when it comes to internal structures. What if your gene of interest is involved in forming the gut, or a particular set of muscles? One way you could go about observing internal structures would be to dissect your flies, but this has its limitations – it requires good manual dexterity, and has the added risk of tearing, ripping or otherwise mutilating your specimen. You could use in situ staining or florescence microscopy, but what you end up with is a flat 2-dimensional image that might not reveal all the details that would be present in three dimensions. Using a confocal microscope will give you good resolution, but generally use high magnifications that will not allow you to view your whole specimen at once. The paper by Jährling et al details a technique using ultramicroscopy that allows for an entire 3D reconstruction of a specimen, complete will internal structures visualized in situ.
The basic procedure goes like this: they began by "chemically clearing" their specimens – that is, using a series of chemical washes and incubations, they removed almost all colour from their specimens. They were left with flies which were nearly transparent. This would allow the internal structures to be visualized. The specimens were then mounted on an ultramicroscope, and using a laser, they took a series of 597 images, beginning at the top and moving down through the vertical plane. Once the images had been taken, they used specialized software to layer the images on top of one another to reconstruct a 3-dimensonal model. Since the flies were transparent, the model allowed for the visualization of internal structures as well as the specimen's surface. Using this technique, you can easily visualize internal structures that might be of interest to you without ever having to dissect your specimen or rely on 2-dimensional imaging techniques.
This technique really becomes powerful when coupled with fluorescent microscopy. Imagine you're convinced that your gene of interest plays a role in the development of the fly's gut. Attach GFP to a gut-specific promoter, insert the construct into your flies and then image them. What you'd get is a perfect 3D model of the fly's gut, easily distinguishable from surrounding tissue. Any phenotypic effects would be easy to observe! Using this technique, you could easily, quickly (the authors state that it takes about 30 minutes from start to finish) and reliably visualize any internal structure you wish. Pretty cool, no?
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References:
Jährling N, Becker K, Schönbauer C, Schnorrer F and Dodt H-U (2010). Three-dimensional reconstruction and segmentation of intact Drosophila by ultramicroscopy. Front. Syst. Neurosci. 4:1. doi: 10.3389/neuro.06.001.2010
It would seem that debunking Youtube creationists has become a hobby of mine. This week, I present a fellow by the name of MyGhettoGospel (I guess Jesus was into gangsta rap), who, for the sake of brevity, I'll refer to as MGG henceforth. MGG believes that biology can prove that the Bible is true, and presents his argument in the video below.
His argument is as follows: the Bible tells us that God "holds everything together"1. If it were not for God, he claims, everything would simply fall apart and the universe would be devoid of any sort of structure - and this includes people. Luckily for us, MGG says, biology provides evidence that this is indeed the case. The cells in our bodies are held together by adhesion molecules. One class of these molecules are laminins (or 'laminin's' as MGG seems to prefer). And, Great Scott, these molecules look like crosses. MGG has a picture and everything! What else could this be but the indelible mark of the Creator? A sound theological argument. Too bad it isnt reality.
MGG's argument falls apart for a variety of reasons. The first, and probably the biggest flaw in his argument is that laminin doesn't actually look like a cross. In his video, MGG states "If you look up laminins in any scientific medical piece of literature, this [the cross shape] is what you will see'. Well, I called MGG's bluff on this one and took a brief perusal through the literature. Here is an image taken from Denzer et al (1998)2:
Look much like a cross to you? Maybe, if it were constructed by a carpenter in a drunken stupor. How about this image from Beck, Hunter and Engel (1990)3:
Nope, still not a cross. I guess the literature does not support MGG's argument as strongly as he thinks. His error is in mistaking diagrams of laminin, like the one he presents, for the molecule's actual physical appearance. Diagrams of any molecular structure are stylistic representations. They are always drawn in a way that makes it easy to understand the basic structure of a molecule - where the domains are in relation to one another, how many peptide chains comprise the molecule and how they are linked together, for instance. They are not meant to be taken as representing precisely what the molecule looks like. There is always some creative liberty taken when designing a diagram. Laminin does not have a rigid cruciform structure. It resembles a cross only vaguely.
This vague cross-like shape shouldn't be in any way surprising to start with. A cross shape is very simple; it's just two lines running perpendicular to one another. Given the number of different types of proteins in the body and the variety of conformations that they can take on, it would be incredible if there weren't any proteins that resembled crosses. It can easily occur naturally and randomly. Imagine tossing toothpicks across a table. Given enough toothpicks, you're bound to find some that fall to form a cross. Would anyone argue that God had a role in this? I guess Divine Toothpicks aren't marketable.
But even if laminin did take on a rigid shape, who is to say that it depicts a cross? It could look like many things. Rotate it 90° and it looks like a dagger. I think you'd be hard pressed to find anyone who would claim this is a molecular representation of a Sikh's kirpan, and therefore Sikhism is the one true religion. The cross argument is equally absurd.
Another reason why MGG's argument is bunk is that it takes for granted the shape of Jesus' execution device as a cross. The shape of the cross has been branded into the public conscience for centuries but there is little historical reason for this. Implements for crucifixion took a variety of shapes. Writing 75 CE, the Roman historian Josephus commented that crucifixion was done in a variety of ways4. Indeed, crucifixion was sometimes done using wooden devices shaped like a T, like a Y or even like an X, as well as using the familiar cross shape. Is there any reason to believe that Jesus was crucified on a cross? Surprisingly, no. The word used in the Bible to describe Jesus' execution implement, in the original Greek, was "σταυρός" (stauros). This is translated as "upright stake" or "wooden post", indicating that he was nailed to a simple, single upright beam (known as a crux simplex). Plutarch and Lucian describe the stauros as having the form of the Greek letter Tau, or T. Neither of these interpretations can be taken as meaning a cross. So if Jesus being crucified on a cross is of dubious nature, so too is the laminin argument. If Jesus actually died on a simple wooden pole, then a cruciform molecule has no significance.
MGG's argument is also problematic theologically. The structure of laminin predates the supposed crucifixion of Christ by many millions of years. Even by Creationist standards, the crucifixion did not occur until thousands of years after Creation. Why would God decide to use a design based on the cross, then? Did he have foreknowledge that Jesus was to be crucified? This would indicate that Jesus was destined to die on the cross for mans' sins. And if Jesus was destined to die on the cross, then mankind was destined to sin. This sort of deterministic implication is at odds with the rest of theology, which claims that God gave man free will and that sin is a choice. MGG's argument implicates the opposite. Which is it, MGG? You can't have it both ways.
In essence, MGG's argument fails. Not only does laminin not resemble a cross, but even if it did, it wouldn't make any sense to interpret it as as sign from a Creator. Creationists, please stop polluting molecular biology with your nonsense. Besides, we all know who really holds us all together.
1. "The Son is the image of the invisible God, the firstborn over all creation. For in him all things were created: things in heaven and on earth, visible and invisible, whether thrones or powers or rulers or authorities; all things have been created through him and for him. He is before all things, and in him all things hold together" Collosians 1:15-17
2. Alain J. Denzer et al. Electron microscopic structure of agrin and mapping of its binding site in laminin-1 . The EMBO Journal (1998) 17, 335–343, doi:10.1093/emboj/17.2.335
3. Konrad Beck, Irene Hunter, and Jürgen Engel . Structure and function of laminin: anatomy of a multidomain glycoprotein . The FASEB Journal . 4(2), 2148-2160
I love DNA. It is a wonderfully complex molecule and the mechanisms whereby genetic information is stored and accessed is fascinating; and yet, at the same time, the basic premise by which is works - the "central dogma" of molecular biology - is beautifully simple. There is little wonder why DNA has caught the eye of the public in a way that few other biological compounds have. This fascination with DNA has necessitated trying to explain the concepts underlying genetics to the public. Therein lies a problem for scientists and science journalists: how to convey the intricate and often confusing workings of science in a way that is both interesting and easy to understand for the layperson. The one tool brandished about the most is the metaphor. Unfortunately, the metaphor can be dangerous, and there is no better example of this than those metaphors used to explain DNA. Two unfortunate metaphors for DNA have been devised: the idea that DNA functions as a "blueprint" and the idea that DNA functions like a "computer code".
The 'blueprint' metaphor is especially poor. Consider what a blueprint is, exactly. It is a scale schematic used to represent a structure. If you have a blueprint of a hotel, you have a schematic of how to build that hotel. The blueprint tells you everything you need to know - how high the ceilings are, how long each wall is, how many steps are in each flight of stairs. Furthermore, you know that 1 inch on the blueprint represents, say, 1 meter in the actual hotel. From the blueprints, you can precisely construct the hotel. But there is more to a blueprint than this. The information conveyed in a blueprint works both ways - you can use a blueprint to construct a hotel, and from a fully constructed hotel, you can derive a blueprint. If a wall in the hotel is 3m in length, you can draw a wall on the blueprint 3 inches long. The information is reversible. You can go from blueprint to structure and from structure to blueprint.
This is where the analogy with DNA fails. DNA does not work as a blueprint because the information is not reversible. DNA does contain information necessary to construct an organism, but if you examine a fully formed organism, you cannot reconstruct the original DNA sequence. You cannot measure the length of a nose or determine the colour of an eye, and then write out the specific sequence needed to create these features. This is a very important aspect of a blueprint, and DNA does not meet this requirement. Rather, DNA acts more like a recipe. A recipe tells you what ingredients you need and in what manner to combine them in order to create a pie. But if you have a pie, you cannot examine it, even in the most minute of detail, and work out the exact recipe that was used. The information contained in a recipe is not reversible, just as the information spelled out by our genes is not reversible.
The 'computer code' metaphor is also a poor one, for multiple reasons (this particular analogy was popularized by Discovery Institute lackey Stephen C. Meyer). The way a computer code works is that the exact sequence of the code - the precise order of the binary 1s and 0s - spells out exactly what operations the computer must perform. But in genetics, the sequence is only part of the picture. Just as important are genetic regulatory networks - which genes are turned on at what times and in combination with which other genes. Phenotypes are not simply the result of particular gene sequences but the result of specific gene-gene (or gene network-gene network) interactions.
But DNA bears little relation to a "code" in a more fundamental way. Consider exactly what a "code" is. A code is a system of arbitrary symbols used to represent ideas and objects. In a sense, language itself is a "code"; the symbol "dog" represents that furry tetrapod with a waggly tail, for example. In a code, the symbols themselves have no inherent meaning. The letter "d" is meaningless by itself, as are the letters "o" and "g". It is only in combination that they derive meaning, and their meaning is derived from the idea that they represent. Furthermore, they only have meaning because we give them meaning. "Dog" is merely the label we apply to Fido; in a universe without sentient beings, "dog" would be meaningless. DNA does not fit this description at all. DNA is not arbitrary in any way; each letter of the genetic "code" is an actual biological compound. ACCGTCGA might be the gene for determining how long your toe hair is, but unlike a code, A, C, T and G each have their own non-arbitrary meaning. And this meaning exists independently of human sentience - the sequence of nucleotides does not have meaning only because we give it meaning. It would have meaning even if humans didn't exist at all.
What DNA is, is a polymeric chemical that follows a dynamic chemical process, governed by universal physical rules. It is only a "code" in the same sense that nuclear fusion is a "code" for how stars produce light
So why am I taking the time to mention these things? The reason is because both these weak metaphors have been abused time and time again by creationists (and particularly the Intellignent Design IDiots). Just recently, the video below was posted to Youtube by Nephilimfree, who you may recall from my last blog post (to which he made no attempt to refute, despite having been made aware of my critique - something that should probably come as no surprise to anyone, given the tendency for creationists to retreat with tail planted firmly between their legs when presented with cold, hard, scientific fact). This latest video does not appear to be made by Nephy himself (though he gives no credit to the video's creator), but is nonetheless filled to the brim with that Nephy-brand distortion of science. While it is significantly shorter than his last few 14-minute diatribes, it might still result in significant impairment to your mental faculties, so watch at your own risk.
The video wastes no time in misleading the viewer, tossing out the "blueprint" metaphor 39 seconds in: "DNA contains the blueprint of all life and is by far the densest information storage mechanism known in the universe". For reasons stated above, we know this metaphor is misleading at best and deceptive at worst. But it continues: "The program code and design of such an incredible system indicated a supremely intelligent designer".
Now, a claim like that one is pretty bold, and would require pretty strong evidence to rationally accept it as fact. So what kind of evidence does the video provide? The answer, really, is "none". It immediately cuts to clips of creationist talking heads (Ken Ham, Dave Hunt, and the like) who reiterate one point: "DNA is a code, and codes are information, which only comes from intelligence". Yet, at no point do they present one shred of evidence for why this is the case. They expect the viewer to simply take what they say as being true. Here we have a major distinction between science and creationism - any scientific claim will be backed up by evidence and cite sources explaining why the claim is true, whereas creationism makes assertions which they simply expect you to believe.
The video proceeds to give some details of DNA - it is self-replicating, has error-correction mechanisms ("there are special proteins called enzymes...making repairs" announces Frank Sherwin - a statement that could only be more generic had he said "there are chemicals that do stuff"), etc. But throughout, a unifying theme is repeated - "these things are complex and only God can produce complexity". But again, they provide no reason why we should believe this is true. Perhaps it is left up to our imagination.
What the video boils down to is that creationists make two claims about DNA: 1) that DNA is a "code", and 2) information/complexity (via the genetic code) can only come from an intelligent designer. Both these claims are really nonsense.
Calling DNA a "code", as explained above, is simply incorrect. DNA is not a code in any sense of the word. But let's assume for a moment, that DNA is a code written by God. If this were the case, then God could definitely benefit from taking an introductory computer programming course. God seems to be an awful coder. DNA is very error prone, and the code is regularly mistranslated and copied incorrectly. Different organisms have similar functions, but use different coding sequences. Some organisms contain the code for functions they don't even use, and the majority of code in any given organism is completely non-coding! For an all powerful supreme being, his code is awfully amateurish.
The argument that "information and complexity can only come from intelligence" is also absurd. To begin with, whenever creationists fling around the term "information" they never define what it is they mean by the term. "Information" can mean different things in different contexts. To a creationist, information is some amorphous concept, never, or only vaguely, defined. The idea that "information" cannot be arranged by nature is also silly. Consider the following situation. A friend says to you, "The sun has to have been created by an intelligent creator. There is no other way to explain sunlight." "Don't be silly," you retort. "The sun is a burning ball of hydrogen which emits energy with wavelengths in the visible spectrum." Unfazed, your friend replies, "That is nonsense. Consider the sources of light we have here on Earth. We only ever see light from light bulbs. Light bulbs do not arise naturally! They are the produce of man made design. We never see light occurring naturally. The sun has to have been intelligently designed. Chemicals cannot just come together and "randomly" create light!". Such an argument is not unlike that creationists use to explain genetic information. They claim that genetic information has to have been designed because information does not arise spontaneously; but the claim that information does not arise spontaneously assumes that genetic information was designed! Once again, a creationist argument is little more than tautology.
In the end, the argument presented in Nephy's little video can basically be paraphrased as "Look at DNA! Look at it! Isn't it complex?! And look at cells! They are soooooo complex!", and then baselessly ascribing that complexity to God. This is, of course, patently untrue. There are many examples of complexity arising through completely naturalistic mechanisms. Snowflakes are a perfect example of this. Do creationists really think that their God spends time making each individual snowflake? What about crystals? Pour some sugar into hot water and suspend a string in it, and before long, you have beautiful and complex crystalline growth. This is an entirely natural process - complexity without the intelligence.
Complexity is not the hallmark of design. DNA is not a blueprint nor is it a computer code. And once again, Nephilimfree is not correct.
