Making the rounds on the blogosphere and the news sites today is the announcement that researchers have discovered the "7th and 8th bases of DNA". This announcement comes from a paper published online on Science's pre-print server1, Science Express by researchers at the University of North Carolina School of Medicine, and most of the news reports seem to be based on an article posted to Science Daily. The article reads:
"For decades, scientists have known that DNA consists of four basic units -- adenine, guanine, thymine and cytosine. Those four bases have been taught in science textbooks and have formed the basis of the growing knowledge regarding how genes code for life. Yet in recent history, scientists have expanded that list from four to six. Now, with a finding published online in the July 21, 2011, issue of the journal Science, researchers from the UNC School of Medicine have discovered the seventh and eighth bases of DNA."
Oooh! Exciting! What are these bases, exactly?
"These last two bases -- called 5-formylcytosine and 5 carboxylcytosine -- are actually versions of cytosine that have been modified by Tet proteins, molecular entities thought to play a role in DNA demethylation and stem cell reprogramming."
So, wait a second. These "new" bases are only modified forms of cytosine? So what? This is no big deal at all. There are well over a dozen known modified bases. Here, let me list a few:
5-hydroxymethylcytosine
5-hydroxymethyluracil
N4-methylcytosine
7-methylguanine
N6-methylcytosine
β-D-hydroxymethyluracil
Need I go on? If we're counting modified bases, then there are perhaps two dozen or more known bases. Why do 5-formylcytosine and 5-carboxylcytosine get the elevated status as the '7th and 8th' bases, when there are so many more modified bases that seem to have gone ignored (and who, for that matter, gave 5-methylcytosine and 5-hydroxymethylcytosine the distinction of being the 5th and 6th)?
Is the discovery of 5-formylcytosine and 5 carboxylcytosine interesting and exciting? Yes, most definitely. Are they the "7th and 8th" bases of DNA? Nope, not at all.
Ito, S., Shen, L., Dai, Q., Wu, S.C., Collins, L.B., Swenberg, J.A., He, C., and Zhang, Y. Tet Proteins Can Convert 5-Methylcytosine to 5-Formylcytosine and 5-Carboxylcytosine. 2011. Science Published Online 21 July 2011 doi:10.1126/science.1210597
So the Canadian government has decided to give our bills a makeover. Gone are the days of money made out of cotton! A new era of synthetic polymer bank notes has arrived. They look pretty cool, which is good. Supposedly, these notes are harder to counterfeit, which is even better. And the $100 bill is a celebration of science, which is even more awesome. The reverse side of the bill shows a bottle of insulin, a lady working at a microscope, and a strand of DNA, as shown below.
Wait a second. Something looks wrong here. Let's take a closer look...
That helix is left-handed! DNA is a right-handed helix, not a left-handed helix. I applaud the Government for making the bill science-centric, but really, how hard would it have been to get the art accurate? The left-handed helix mistake is incredibly common, but that's really no excuse.
In last week's This Week In Science, I summed up a paper published in Scicence by Li et al.1 which was hyped up as being a challenge to the Central Dogma of molecular biology. The authors compared the RNA sequences from numerous individuals to the original DNA sequences they were derived from. What they found were a multitude of sites where the RNA sequences differed from that which would be expected given the original DNA sequence. Moreover, these variations were shared across individuals, indicating that they were not likely due to random mutation. Furthermore, the team found proteins that matched the varied RNA sequences and not the DNA sequences. These results suggested that there exists some yet unknown editing step during transcription that alters individual nucleotides in the resulting RNA transcripts.
However, declaring the Central Dogma to be toppled may have been a bit premature. According to Lior Pachter at the University of California, Berkley, the variations discovered by the researchers could be artifacts caused by their sequencing equipment. Many of the sites that were found to contain altered nucleotides lie in regions which are known to often cause RNA sequencing errors. In other words, the variations that the team observed, in many cases, might just be sequencing mistakes.
Further skepticism has been shown by Joe Pickrell at the blog Genomes Unzipped (which I highly suggest reading, as he goes into quite a bit more detail than what I've presented below). He points out that the differences in RNA and DNA that the authors discovered might be false positives created by attributing a particular RNA sequence to the incorrect DNA sequence. For any given DNA sequence, there are bound to be other sequences very similar - even almost identical - to it2. If you are given an RNA sequence, then, how do you determine which of the very similar DNA sequences it is derived from? Unless one takes steps to remove the incorrect sequences, it is very likely that you will end up with a false-positive. It would appear that Li et al. did not take such steps.
Pickrell points out another problem with sequencing and mapping through RNA splice sites. Mammalian genes are frequently alternatively spliced, and a cDNA library like the ones Li et al. used will have multiple isoforms of a gene. When mapping such transcripts back to the genome, you have to keep in mind that the genomic sequence will still contain the introns that have been excised in the mature mRNA transcripts. If you compare the shorter, edited mRNA to the longer, unedited DNA, you're likely to find many differences between the two. Mapping a particular sequence read to the wrong isoform will generate false-positives. Pickrell shows that Li et al. did just this on at least one occasion.
So widespread RNA editing in humans might not be a reality. It's possible that it is, but problems with the procedure used by Li et al. raise many doubts. I'm looking forward to reading the follow-up research. Until then, as perhaps Mark Twain would say, reports of the death of the Central Dogma have been exaggerated.
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)
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
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.
Are you tired of sequencing your gene of interest 800bp at a time? Sick of straining your eyes staring at a fuzzy chromatogram? Fed up with waiting hours for your PCR to finish only to realize you forgot to add ddNTPs to your reaction mix? Well, nex-gen DNA sequencing is for YOU!
Cheesy sales-schtick aside, next-generation DNA sequencing technologies are on the rise (and are poised to soon become current-gen technologies - some already are!). The days of loading your PCR'd sequencing mix onto an automated capillary sequencer may soon be numbered. So, to make the change of power of our mighty sequencing overlords a little easier, this series of posts will be dedicated to how the upcoming technologies work, their advantages over conventional sequencing technologies, and their problems.
Today's post: Pyrosequencing
Pyrosequencing is perhaps the one Next-Gen sequencing technology that is the most like current generation automated sequencing (if you need a reminder on how that works, I've written about it in the past). It still requires primer design, and rounds of PCR, but the method of detection of incorporated nucleotides differs.
Pyrosequencing starts by adding your PCR'd sequence to a reaction mix that contains DNA polymerase, and three important enzymes: DNA sulfurylase, apyrase and luciferase. DNA sylfurylase is an enzyme that converts a pyrophosphate molecule into ATP. Luciferase is an enzyme which uses ATP to convert luciferin into oxyluciferin, resulting in the emission of light. Apyrase's job is to degrade unincorporated nucleotides. Given that the addition of a nucleotide into a growing DNA strand results in the release of a pyrophosphate molecule, keen readers might already see how pyrosequencing works.
With conventional automated chain-termination sequencing techniques, we add all of our dNTPs to the reaction mix at once; they can easily be distinguished because each base has a different fluorescently labelled dye bound to it. With pyrosequencing, however, one cannot toss in all the nucleotides at the same time. Rather, we have to add each one sequentially for each nucleotide in the sequence. That is, we first do a reaction with A, then with T, then with C and lastly with G. We then repeat this cycle over and over until the sequencing reaction is complete (if this sounds confusing, hopefully the diagram and video below will clarify it). Why we do this will be apparent in a moment.
When a nucleotide is incorporated into the DNA strand, a pyrophosphate molecule is liberated1. This pyrophosphate molecule can then be converted by the DNA sulfurylase into a molecule of ATP. Luciferase picks up this ATP2 molecule and uses it to catalyze the conversion of luciferin to oxyluciferin. This chemical conversion results in the emission of a photon. This chain of events, then, means when a nucleotide is added by DNA polymerase to the growing DNA chain, we get the emission of light. A computer with a suitable detector could detect this light, and we would have an indication of when a nucleotide was added in our sequencing reaction.
But if we add all of our dNTPs at once, then how do we know which ones are being ? This is why we only add one nucleotide to the mix at a time. First the reaction is run using dATP. We then add apyrase to remove any remaining nucleotides and repeat with dCTP, and so on. If we add the nucleotides one at a time, then they will be incorporated (or not incorporated) into the sequence one at a time, and consequently we get one light signal at a time.
The light signals are recorded on a chart called a pyrogram. This chart records not only which nucleotides resulted in the emission of light but also the intensity of that signal. If three dTTP molecules were incorporated at once, then there would be three photons emitted and three times as much light; this would result in a triple peak on the pyrogram. From the pyrogram, then, one could easily read off the exact DNA sequence. The figure to the left shows one such pyrogram. The sequence in this example would be GCAGGCCT.
The following video puts the whole process together nicely.
So why would one choose pyrosequencing over automated chain-termination methods? Well, for one, it's cheaper (though, not as cheap as some of the other upcoming next-generation sequencing methods). Practically, it's easier to do, since it doesn't require running through gels or capillaries. Analyzing the resulting pyrogram is also easier than analyzing a chromatogram. Chromatograms can often be spotted with "N"s when the computer cannot tell if the wavelength of light from a dye is one color or the other; however, with pyrosequencing, detection is binary - either a photon is emitted or not - so results are more accurate and clearer.
Though, pyrosequencing does have it's drawbacks. It requires a greater number of PCR cycles than traditional sequencing does, so it may take longer to complete, especially for longer sequences. Currently, a typical read of sequence data from pyrosequencing is about 300 to 500bp - shorter than the typical 800 to 1200bp you get from chain-termination methods. This, however, is likely to improve as the technology advances and becomes more refined. The shorter reads, though, make it tough to sequence genomic regions containing high amounts of repetitive DNA.
So that is pyrosequencing in a nutshell. Next time: Helicos sequencing!
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1. NTPs are triphosphates (that's what the TP stands for!), meaning each nucleoside (base+sugar) is attached to a phosphate molecule. To add a nucleotide to a growing DNA strand, the reaction requires an input of energy. This energy comes from the breaking of the triphosphate chain in each nucleotide; two phosphates are broken off and released as a pyrophosphate (PPi) molecule, and the remaining portion of the nucleotide is attached to the hydroxyl group on the 3' carbon of the previous nucleotide in the sequence.
2. Observant readers might be confused here. Since luciferase requires ATP to convert luciferin to oxyluciferin, won't this cause a problem when we add dATP to the sequencing reaction? Won't there be competition between DNA polymerase and luciferase? Well, if you thought that, then you'd be right! For this reason, we use dATPαS instead of dATP for pyrosequencing. This molecule has a sulfur atom attached to the α phosphate of the nucleotide, and cannot be used as a substrate by luciferase. Problem solved!
I recently joined Yahoo! Answers to give me something to do on my lunch breaks at work by answering peoples' questions about molecular biology and genetics (a niche that needed filling because it only took me a week to become a "Top Contributor" in biology). Yesterday, there was a challenge put towards "evolutionists" (ugh, how I hate that term): give the one (1) piece of evidence you would put forth to a creationist to try and sway his/her opinion on whether humans descended from earlier primates. There is literally a whole boatload of evidence to support man's descent from earlier primates, but picking the single piece of evidence to sway a creationist's opinion was tough. I thought about it for a minute and decided to present the case from Chromosome 2. I thought I'd reproduce my answer here:
You want one convincing proof? Consider this:
I'm sure you've heard that humans and chimpanzees have the vast majority of our DNA in common. You're also probably not convinced by this argument ("I don't understand...so what if two organisms share the same genes? How does this prove that they came from the same lineage?"). But for now, forget about how very similar we are in our genetic sequence and let's focus on our chromosomes.
If you need a refresher, remember that the number of chromosomes a species has tends to stay the same from generation to generation. A fruit fly has four autosomal chromosomes and one pair of sex chromosomes; it's offspring will all have the same number. What about us humans? We have 23 pairs of chromosomes; 46 chromosomes in total. If you took a karyotype - that's a display of all the chromosomes in a cell - of an ape (I know you're skeptical of humans being primates, but lets call 'em primates for now) you'll notice something different from human chromosomes: there's two extra! Apes have 48 chromosomes.
You might wonder how this proves we evolved from an ancestral primate. You might even suspect that it is evidence against such a claim, since an ancestral primate would have had 48 chromosomes, and that number would have likely stayed constant down the generations, while in us, it's different. Well, this information alone does not prove much. But let's take a look at what the genome sequence shows us.
The sequence of the human genome showed an interesting fact about our Chromosome 2. The area around the very centre of chromosome 2 (known as a centromere) looked an awful lot like telomeric DNA. Telomeres are the regions at the very ends of chromosomes; what were they doing in the centre of chromosome 2? Furthermore, each arm of Chromosome 2 had what appeared to be their own centromeres. Chromosome 2 was looking to be quite an oddity. No other human chromosome displayed these characteristics.
Once the chimpanzee genome was sequenced, things got even more interesting. One of the chimpanzee's chromosomes was pretty much identical to the top half of the human Chromosome 2. Another chimpanzee chromosome was nearly identical to the bottom half of Chromosome 2. On top of this, the banding pattern of these two chromosomes (as well as the same chromosomes in many other species of primates) was a complete match to the banding pattern of Chromosome 2.
Coincidence? Not likely. What this is, is evidence of a chromosomal fusion. An ancestral primate, ancestor to humans, chimpanzees and apes, had 24 pairs of chromosomes. Eventually, this lineage diverged: apes and chimps went one way and we humans evolved along a separate path. But something interesting happened in the lineage that was to become humans: the two extra chromosomes from that ancestor fused together end to end to become human Chromosome 2. This is why our Chromosome 2 has what appears to be telomeres in its centre, and what appears to be two extra centromeres, one on each arm.
The only way to explain Chromosome 2's odd characteristics and similarity to other primates is with a chromosomal fusion. And the only way this could be possible is if we were descended from a common primate ancestor.
So, I put the question to you: if you could give only one single line of evidence for man's primate ancestry to change a creationist's mind, what would it be?
But myostatinmutations are also found elsewhere. Meet the Belgian Blue.
The Belgian Blue is a breed of cattle that has been selected for a naturally occurring myostatin mutation. The result is, quite obviously, a rather beefy (pardon the pun) cow that produces lean meat (since the mutation also interferes with fat deposition) and lots of it.
Perhaps it's the carnivore in me speaking, but I think that might be the most awesome breed of cattle. Ever.
Now I have a craving for a big, juicy steak...
A nod to Sentient Developments for bringing this massively delicious specimen to my attention.
A common argument among creationist types is that evolution is impossible because it requires an addition of genetic information to a genome, which, they say, never happens. Instead they posit that genetic information is only ever lost through mutation A mutation in a gene encoding for alcohol dehydrogenase, for instance, results in the loss of the ability to metabolize alcohol. This represents a loss of genetic information. Further, they claim that beneficial mutations are exceedingly rare (or impossible) - a claim that is incredibly fallacious - and because of this, evolution is impossible. Some creationists have even claimed that this question stumped Richard Dawkins himself, however this has been shown to be an outright hoax.
The most obvious problem with this claim is that what is meant by "information" is never actually defined by creationists. Do they mean new genetic "instructions" - new and different genes being added to a genome? Do they mean new physical DNA being added to expand a genome? "Information" is quite a vague term, and can mean a multitude of things.
I would assume, however, in most cases, "information" refers to new genes being "added" to a genome, since genes ultimately supply the "information" or "instructions" an organism needs for body plan organization, carrying out metabolic processes, growth and development. And if the claim really is that there are never new genes added to a genome, then the claim is blatantly false.
Adding new "information" to the genome is actually quite simple and very common in the natural world (that is, outside the laboratory). It's a little process called gene duplication.
I won't get into all the nitty gritty details about the various ways that gene duplication occurs, because they're not all that relevant to the topic at hand, but common causes of gene duplication are homologous recombination, retrotransposition, or simply errors in DNA replication (the DNA Polymerase slipping back along the DNA strand, for instance). In either instance, the result is an extra copy of a gene is present in the genome.
A great example of gene duplication are the human globin genes. We do not simply have one gene for "hemoglobin"; rather, humans have a variety of hemoglobin genes: α-hemoglobin, and β-hemoglobin are the two expressed the most in adults, with ε- and ζ-hemoglobin expressed in the embryo, and γ-hemoglobin expressed during all stages of development. It should be of no surprise that all of the hemoglobin genes, despite being expressed at different times during the human life cycle and having slightly different functions, are all very related. The various forms of hemoglobin have arisen through gene duplications. According to Ross Hardison1,
"In the distant past, some ancestral - probably single-celled - organism had one hemoglobin gene, and therefore one kind of hemoglobin protein. But at some point, this gene was duplicated, so that each of the resulting daughter cells carried two identical copies of the ancestral hemoglobin gene. Gradually, during successive cell divisions, small variations in the sequence of nucleotides - the subunits that make up a gene - started to appear. In this way, the two genes that started out identical acquired sequence differences and later, functional differences. It is quite likely that additional hemoglobin genes were acquired the same way, by gene duplication followed by modifications in the nucleotide sequence."
I can already hear the cries of the creationists. "But," they proclaim, "this doesn't show evolution at all, for the different hemoglobin genes are still all the same kind!" (Oh how I hate that dreaded "kind" word). This is where gene duplications can get interesting. Once a gene duplication occurs, you have an extra copy of whatever gene that's been duplicated in your genome. This essentially works like a "backup" copy of the gene. Since a lot of mutations are deleterious (but not most mutations, as the creationists would have you believe), then having this backup copy gives a clear advantage - one copy is free to be mutated without the organism encountering any deleterious effects. These duplicated genes gain mutations at a faster rather than other genes, since potentially disastrous mutations in them won't kill the organism, allowing them to be passed on to future generations and sustain even more mutations (compared to a non-duplicated gene, where a disastrous mutation kills the organism, so neutrally and unmutated copies are what get passed on to future generations).
What does this mean? It means that the gene now has the potential to take on new functions, different regulation, etc. In essence, the duplicated copy has the potential to become an entirely new gene - one that gives an entirely new function - such as being able to metabolise a new food substrate, break down toxic compounds or grow larger and more quickly. New genetic "information" has been added to the genome.
It amazes me that the "no new genetic info" claim is still such a common one among creationists. Gene duplication as a major player driving evolution has been accepted by the scientific community for the better part of the last 100 years2. Indeed, Susumu Ohno had claimed back in 1967 that gene duplication is the single most important factor in evolution3. The reality is that new genetic "information" is added to genomes - yours, mine, every living organism's - quite easily and quite commonly.
EDIT: And it can get even easier. Prokaryotic organisms, like bacteria (and even some eukaryotes like amoeba) can take up bits of exogenous DNA (that is, DNA that is simply floating around in their environment), adding "new information" to their repertoire almost instantly!
------------------------------------ 1. Hardison, R. (1999) . "The Evolution of Hemoglobin" American Scientist 87.2: p126 2. Taylor, JS. & Raes, J. (2004). "Duplication and Divergence: The Evolution of New Genes and Old Ideas" Annual Review of Genetics 9: 615-643 3. Ohno S. 1967. Sex Chromosomes and Sex-linked Genes. Berlin: Springler-Verlag. 192 pp.
The Gene of the Week is a new feature that I've decided to bring to my blog. Each weekend I'll (try to) write a bit about a gene and it's related gene product that I think is pretty cool.
This week's gene is FOXP2, a gene that has been implicated as having a role in the development of language skills, and is likely to have played a major role in shaping the early evolution of Homo sapiens.
FOXP2 is a member of the Forkhead Box gene family (called "forkhead" after the prominent helix-turn-helix motif that resembles a forked head). It's located (in humans) on the q-arm of chromosome 7, and has a 2285bp transcript. It's gene product, the FOX P2 protein, is fairly large, at 715 amino acids in length. The gene is required for the proper development of the brain and the lungs, but where the gene shines is it's involvement with speech and related processes.
The history of the gene is actually quite interesting. Around 1990, a family known simply as the KEfamily, caught the scientific community's attention. The family was of particular interest because, over the previous three generations, around half of the family members developed severe problems with speaking - to a point that their speech was quite incomprehensible and they had to rely on sign language to communicate - as well as other physical and mental handicaps. A pedigree of the family and the disorder showed a pattern of inheritance suggestive of a mutation in a single, autosomal dominant gene.
It was not until 1998, when Fisher etal.1 did a linkage study and narrowed the location of the gene to a small region of chromosome 7 (7q31), and named the hypothetical gene SPCH1. Three years later, in 2001, Laietal.2 made an interesting discovery. Working with a patient that exhibited a similar to that of the KE family, they discovered that the patient had a chromosomealtranslocation affecting chromosome 7. In fact, the break point of the translocation was in the very region that Fisher and colleagues pinpointed in 1998. Going back to the KE family, the team found that the same gene that was broken in their patient had a point mutation in all of the affected members of the KE family and was not found in any of the unaffected members or control groups. In effect, they had found the gene that was causing the disorder in the KE family. The popular media caught wind of this discovery and, unsurprisingly, overexaggerated the finding with claims of a "gene for language", implying that this was a gene unique to humans that allowed us to talk - a claim that was blatantly false.
The gene that Lai and fellows found was a member of the FOX gene family - FOXP2.
Since then, lots of work has been done on the FOXP2 gene. It's been shown to affect vocalization in mice pups, song learning in finches, and even in the development of echo-location in bats. It has also been found that the gene is widely conserved, from fish to alligators to humans. However, what makes the gene particularly interesting from an evolutionary standpoint is that the human form of the gene is a bit different from the rest: it differs from the form of the gene found in other primates by two amino acids. It is speculated by some researchers that this difference is what lead to the development of language in humans, though a mechanism for this is yet unknown. Other researchers are of a different mind, claiming that the two amino acid difference is unlikely to have resulted in the development of language, but rather, a difference in gene regulation - when and where the human form of FOXP2 is expressed - is a more likely origin.
Much work remains to be done on FOXP2. It is a known transcription factor, but the genes it regulated are still unknown. Investigations into its role in evolution will undoubtedly continue. Be sure to keep your eye out for developments in this gene; it's bound to shed some light on the recent evolution of our species.
----------------------------------------------------------------- 1. Fisher etal, Nat Genet 18, 168 –170 (1998) 2. Laietal, 'A forkhead-domain gene is mutated in a severe speech and language disorder'Nature 413, 519 - 523 (2001)
For further reading and more details, see: http://www.evolutionpages.com/FOXP2_language.htm http://en.wikipedia.org/wiki/FOXP2 http://www.genenames.org/data/hgnc_data.php?match=FOXP2 http://www.wikigenes.org/e/gene/e/93986.html http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=nuccore&id=219518945
