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Article Biological , Molecular , and the Origins Debate Jonathan K. Watts Jonathan K. Watts

Biomolecules contain tremendous amounts of information; this information is “written” and “read” through their chemical and functions. A change in the information of a is a change in the physical properties of that —a change in the molecule itself. It is impossible to separate the information contained in from their structure and . For such as DNA and RNA, new information can be incorporated into the sequence of the molecules when that new sequence has favorable structural and functional properties. New biological information can arise by natural processes, mediated by the inter- actions between biomolecules and their environment, using the inherent relationship between structure and information. This fact has important implications for the generation of new biological information and thus the question of origins.

traveler is checking in for a flight code or printed text, we expect A and her bags are slightly over that similar devices containing different the weight limit. Without hesi- information will have similar physical tating, she pulls out her iPod. It is very properties. By contrast, different devices heavy, she explains to the check-in agent, may contain the same information in since it contains thousands of songs. She spite of their dramatically different phys- deletes most of the music, repacks the ical properties (for example, the printed iPod, and reweighs the bags—which are and online versions of this article). now well within the weight limits. But biological information is quite Or consider a kindergarten student, different. This article will show that to write letters. He writes a there is a fundamental difference wholepageofA’swithnotrouble.Next between biological information and he wants to practice writing the letter G. abstract information such as computer But after a few G’s are written, they code or text: the biological information seem to want to fold onto each other, cannot be separated from its structure. as though he were writing on the sticky The structure and reactivity of bio- side of a piece of tape. Each new G molecules can give rise to new informa- he manages to add contributes a new wrinkle or fold, until eventually he gives Jonathan Watts is a postdoctoral fellow in the Departments of and at the University of Texas Southwestern Medical Center at up and decides to practice writing a less Dallas. He received his BSc in from Dalhousie University (Halifax, troublesome letter. Canada) and then spent a year on mission in Côte d’Ivoire before returning to and obtaining his PhD in chemistry at McGill University When we laugh at these two impos- (Montreal, Canada) in 2008. His research interests center on the chemistry, sible stories, it reveals how deeply, chemical , and therapeutic applications of . He has almost reflexively, we tend to feel that published eighteen papers. Jon and his wife Katie have two preschool children, information should be distinct from Liam and Lydia. He enjoys music and often leads worship at his church. physical properties. At least in terms of Correspondence can be sent to [email protected].

Volume 63, Number 4, December 2011 231 Article Biological Information, Molecular Structure, and the Origins Debate tion without the direct input of an intelligent agent. differently in (i.e., they exert different Thus we need to be careful when analogies from the functions). world of or literature are applied to bio- logical information. This is important in terms of the Some of my colleagues have made various debate on the origin of . chemically modified analogues of the sequence GGTTGGTGTGGTTGG.4 Since this sequence con- tains only one half of each possible Watson-Crick The Information-Structure basepair,onemightexpectthatitwouldbehave “properly” and exist as a nice unstructured line of Duality of Biomolecules chemical “letters.” On the contrary, it folds into a Discussion of biological information is often limited very complex structure having nothing to do with to the DNA (or RNA/) sequence, which Watson-Crick base pairing (figure 1c).5 superficially looks much like the kinds of abstract information we are familiar with. When the human The two stories we began with were not chosen at sequence was published, biology was said random. Separating and characterizing biomolecules to have entered an information age. Stephen Meyer bytheirmass,forexample,isoneofthesimplest begins his book Signature in the by quoting from ways to analyze their information content. After sources as diverse as Bill Gates and synthesizing an , I first analyze it by who find that “the code of the is (here, my desired sequence and uncannily computer-like.” Meyer’s next question is any impurities that may be present are separated highly pertinent: “If this is true, how did the informa- according to their mass as they are pulled through tion in DNA arise?”1 a gel by an electric field). Then, before carrying out experiments with the oligonucleotide, I inject a small While I enjoyed reading much of Signature in the part of each sample into a mass spectrometer to Cell, I felt that the analogy between DNA and determine its mass more precisely. If the mass of abstract information was taken too far. The issue is a synthetic oligonucleotide is correct, we can gener- that biological information is not abstract: it is allyassumethatthesequenceiswhatwewere always mediated and interpreted by physical inter- trying to produce (i.e., the oligonucleotide contains actions. While studying the chemistry and biochem- the expected information).6 istry of oligonucleotides (short sequences of DNA, RNA, and their chemically synthesized analogues), I have often come face-to-face with the frustration Figure 1. that can be caused by forgetting how tightly infor- Some Structures of Oligonucleotides. mation and structure are intertwined. (a) The duplex form of the Dickerson-Drew Some oligonucleotide sequences can be manipu- dodecamer, which is lated easily enough, such as the letters within in equilibrium with an abstract line of text. But other sequences have (b) the hairpin form. One form may predomi- repeatedly reminded me that a DNA sequence is not nate, depending on the just an abstract line of text. For example, a famous experimental conditions and the chemistry of sequence called the Dickerson-Drew dodecamer the sequence. Both are 2 (5'-CGCGAATTCGCG) can bind another copy of based on Watson-Crick itself by classic Watson-Crick base pairing (A-T and base pairing: G with C and T with A. G-C pairs, figure 1a). But under different conditions, (c) An example of a it will instead fold back on itself, forming into highly stable structure a “hairpin” structure while still making use of having nothing to do with Watson-Crick base Watson-Crick base pairs (figure 1b). Various factors, pairing. The G residues including chemical modifications, can favor one arrange themselves in structure over the other.3 While the sequence infor- “quartets” in a stacked planar arrangement. mation is the same, the two structures respond very

232 Perspectives on Science and Christian Jonathan K. Watts

The second story, as you may already have a three-dimensional electron surface with a defined guessed, relates to the DNA bases A and G, adenine shape and regions of positive and negative charge. and guanine. While both are purine bases and are closely related, guanine folds into a much greater variety of structures and binds to itself with high affinity (as in the sequence from figure 1c). It is nearly impossible, using standard biochemical tech- niques, to copy a DNA sequence containing dozens of adjacent G’s. On the other hand, sequences con- tainingdozensofA’sareeasytocopyandareused each day in laboratories around the world (“polyA” sequences similar to these are also added to the ends of all of the messenger RNA in our cells). Figure 2. Three Ways of Representing the Adenine. Left, the letter “A,” as commonly used when discussing the DNA sequence. Center, the of adenine, showing the In a companion article in this issue, Randy Isaac that make up adenine, their spatial arrangement, and the 7 explores the of biological information. He types of bonds that connect them. “R” represents the sugar- points out that when there is an abstract linkage backbone. In keeping with convention, carbon is assumed to be at any corner not labeled with a different between a given type of information and its - letter, and carbon-bound hydrogens are left out. Right, a computed ing, we can readily identify that the information was model of adenine, showing electron surfaces of net positive or directly written by an intelligent agent. In contrast, negative charge ( gray or dark gray, respectively, in the print version of this article; red or blue, respectively, in the PDF version when the linkage between information and its mean- of this article). The model was generated using Gaussian03W ing is entirely physical (for example, molecular and Chem3D. structure, or function mediated through thermo- dynamic interactions), we may not be able to attrib- Figure 2 gives three levels of understanding of the ute intelligent agency as quickly. information conveyed by a single “A” in the DNA sequence. The one on the left looks something like So, in thinking about biological information as it computer code or text, but, in fact, the complex relates to the origin of life, we must be careful with electronic structure on the right is what analogies from the familiar world of computers or and other “information readers” have to interpret. books. The information in a book can be stored There is much more information in this full struc- in multiple physical forms: a large-print hardcover ture, but it is much harder to quantify and looks edition, an electronic PDF version, or even Braille. nothing like text or code. Perhaps surprisingly, When we read it with the appropriate media or taking this more complex view of biological infor- tools, we obtain the same information. In contrast, mation and its connection to structure will make it biological information cannot be separated from easier to see and to understand how new functional its structure. Three different representations of the information can be generated without being directly nucleobase adenine are shown in figure 2. The first written by an intelligent agent. representation, A, is a common abbreviation used in . It is a letter, a symbol, of the bio- logical information carried by adenine. This simple The Generation of representation facilitates and infor- New Sequence Information mation transfer among researchers. In the second representation, the various atoms are specified. from Structural or Functional Much more information is included here—the types Components of Biomolecules of atoms contained in adenine and the arrangement William Dembski8 and others in the intelligent of bonds that hold it all together. would (ID) community9 claim that natural causes are in- be very comfortable with the second representation. sufficient to produce complex specified information. But the readers and writers of biological information Their “law of conservation of information” can, like (enzymes or other nucleic acids, for example) have any law, be disproved if examples are found that to work with something even more complex, some- violate the law. Yet I find that the law as formu- thing much more similar to the third structure: lated by Dembski does not work in the laboratory;

Volume 63, Number 4, December 2011 233 Article Biological Information, Molecular Structure, and the Origins Debate information can and does arise without direct appropriate choice of four vials: one for each of A, intelligent input. T, G, and C. For our , we will adapt the instrument to make a random oligonucleotide 10 Muchoftheresponsetotheideaofsuchalaw sequence by simply combining the four has discussed the information that arises through blocks in a single vial so that all are equally likely 11 processes of and . Others to be incorporated at each coupling step. Repeating have written about the new information generated the synthetic cycle, say fifteen times, would yield by the when it is presented with an oligonucleotide 15 long. There are 12 an antigen. In these cases, information (and associ- 415 (or just over a billion) different 15- se- ated function) is not directly written by an intelligent quences. At a typical synthesis scale (25 nanomoles), agent, but arises from the interplay of an about 10 million copies of each different option with its environment. would be present. So far we have lots of complexity In Signature in the Cell, Meyer restricts his version but no specificity. In other words, there are a lot of 14 of the law of conservation of information to a non- sequences carrying a lot of information, but no use- biological starting point.13 In keeping with this ful, functional information is present because we have context, I will also discuss a nonbiological example not chosen between any of the options. that is commonly encountered in both academic and However, we can provide specificity by selecting corporate research labs. New information can arise sequences according to their structure or function. from the structure of a molecule such as DNA and For example, our pool of random 15-nucleotide se- the molecules it interacts with. quences will likely contain GGTTGGTGTGGTTGG, To begin this experiment, a random oligonucleo- the oligonucleotide from figure 1c. This complex tide is made on an automated synthesizer. structure binds tightly to the protein -clotting These instruments are usually used to make specific factor thrombin. If we wash our entire pool of ran- (nonrandom) sequences, which can be programmed dom oligonucleotides across a sample of thrombin, into the instrument according to what the this sequence will stick more tightly than others (fig- specifies. The instrument goes through a “synthetic ure 3). This is based on a real example: the sequence cycle” for each successive nucleotide in the chain— GGTTGGTGTGGTTGG was not rationally designed adding one nucleotide at a time, drawing from the to bind thrombin, it was discovered by a similar

Figure 3. selection of an oligonucleotide consists, at its simplest, of (a) generating random sequences, then (b) selecting and identifying sequences with the desired properties from the pool. Here we show protein binding as a selection step; the sequences that do not bind are removed as shown in part (c). Those sequences that bind their target may be amplified (copied) and then undergo the selection cycle several more times. In this way, the best candidates can be identified.

234 Perspectives on Science and Christian Faith Jonathan K. Watts

experiment to the one I have just described.15 Yet it specified information. The constant wings are pres- clearly has generated or uncovered a DNA sequence ent both before and after and so do not count against with specified information. the new information generated.

Variations of this technique are commonly used to What about a polymerase used to make develop DNA, RNA, or even with desired new copies of the selected sequences at each amplifi- properties.16 Beyond a simple function such as bind- cation step? First of all, is being made ingtoagiventarget,itcanproducemorecomplex toward enzyme-free amplification of nucleic acids, functions such as of a .17 so an enzyme may someday not be required to The general is called in vitro selection,or amplify our sequence of interest.23 Otherwise, all of sometimes in vitro or SELEX (Systematic thesameresponsescanbegivenatthispoint.The Evolution of Ligands by EXponential enrichment).18 selection of information has already taken place when one Generally, the selection cycle is repeated several sequence binds its target with higher affinity than others; times to improve the -to-noise ratio and to thus the amplification and are again sim- identify oligonucleotides with the very best proper- ply analytical tools. And finally, the information ties. In between each repetition of the selection step, contained within the enzyme is unchanged and the surviving oligonucleotides are copied (“ampli- remains constant throughout the selection; thus its fied”). SELEX-derived sequences have proven their presence does not detract from the fact that new usefulness as probes to bind target proteins and information is being obtained. small molecules alike,19 and have even led to an FDA-approved therapeutic.20 Finally, what about the information put in by designing and executing a series of selection steps? carefully design SELEX experiments, it is Objections Addressed true. However, I think there are at least three why this objection does not stand. Meyer claims that substantial amounts of informa- tion are put in by scientists during an in vitro selec- First, the key selection step actually occurs when tion process, to the extent that negligible net one oligonucleotide binds its target to a greater information is really produced.21 For example, ran- extent than others. This is a purely physical process dom oligonucleotides are often synthesized with and does not depend on investigator input. “wings” attached at either end, consisting of a known sequence. This helps the experimenter to amplify the Secondly, while amounts of information can be selected sequences (copy them in sufficient quantity hard to quantify when comparing different types, it for further use). This amplification is typically done is hard to argue that a short series of manipulations, using information-rich enzymes. And the selection moving liquid from one tube to another, contributes step itself is designed by the experimenter. anything similar to the amount of information con- tained in, for example, a 15- to 60-nucleotide chunk Let us take these objections one at a time, and of DNA of a specific and functional sequence. I will try to explain why either they are not strictly necessary to a SELEX experiment, or they do not Thirdly, it is not always necessary for researchers count as an inappropriate introduction of informa- to intervene at each step, showing the parallel tion. First of all, the wings of a known sequence are between SELEX and putative natural examples of used for making copies of our selected sequences molecular evolution. For example, two groups have and for measuring the sequence information.22 This demonstrated systems for the continuous in vitro 24 is an analytical problem: the sequences with higher evolution of biomolecules. In these two different affinity have already been selected by their binding examples, in place of a series of selection steps, to the protein, and thus we already have a certain a system is designed so that biomolecules (RNA and degree of new, functional, specified information, proteins) are continually optimized through muta- even before we amplify or read the sequences. And, tion and , and the best sequences are pre- of course, whether or not wings of a known sequence served. Continuous in vitro evolution is very closely are present during a selection, a region of genuinely related to natural selection. Thus we have come full random sequence is being selected and yields new circle: in vitro selection steps mimic natural selection,

Volume 63, Number 4, December 2011 235 Article Biological Information, Molecular Structure, and the Origins Debate something that clearly does not require direct much larger and more complex). This information human input. In the simplest SELEX experiment, is mirrored in the structure of a particular oligo- oligonucleotides that confer a needed function (say, nucleotide that folds in a unique way, and the match binding to a target) survive (by being copied and allows the two molecules—DNA and target—to bind. identified). In nature, the functions may be different, We use the relationship between the DNA and the but survival and are still just as rele- target protein to transfer the information into a form vant. Thus the selection carried out by a researcher we can easily amplify, read, and reproduce—a DNA to obtain oligonucleotides with desired properties is sequence. The same principles apply when we select parallel to the selection pressures of the environment an oligonucleotide that catalyzes a chemical reaction onanyadaptingmoleculeororganismwhenanew or binds to a rather than to a protein. generation survives and multiplies. Molecules are constantly interacting with each In summary, the interventions and manipulations other. Most of the time they “bounce off” one by researchers have parallels in natural selection and another, but occasionally they bind together, or even biomolecular evolution—diversification by muta- undergo a chemical reaction with each other. The tion, selection by survival, repetition. The key selec- interactions between molecules are information-rich tion step—that is, the step that specifies information (for example, as any will tell you, sometimes from the complex-but-random starting pool—occurs the reactivity of a molecule can be used to identify by the of a biomolecule with its environ- its structure). So why have I focused this article ment, not by intervention by the researchers. Even on the transfer of information into a sequence of if researchers set up certain conditions, the desired DNA or RNA? Nucleic acids such as these are a won- sequence is unknown by any intelligent agent derful medium for molecular evolution because involved in the experiment. Useful, functional, they are so easy to copy and analyze. No other specified information is generated from a random type of complex molecule that we know of can be starting point. synthesized chemically, copied enzymatically, and sequenced so readily. Is the amount of information generated in a SELEX experiment so small as to be negligible? A specific However, various creative researchers have none- 20-nucleotide sequence corresponds to 40 bits of theless found ways to evolve other types of mole- information.25 There are hundreds of examples of cules and reactions in the laboratory. For example, functional oligonucleotides generated by in vitro one strategy is to tether reactive molecules to short selection.26 Thus in vitro selection experiments have pieces of DNA: when two particular groups are generated thousands of bits of information over the joined under a particular set of reaction conditions, past two decades. theyleaveatraceintheDNAsequencethatcan be amplified and measured.28 This has led to the discovery of new types of chemical reactions.29 Where Does the Information Come From? SELEX, Serendipity and At the end of a SELEX experiment, a biomolecule Complexity contains more information than the researchers put SELEX experiments are so useful precisely because of in. Is there another source for this information? their ability to capture so much information. In fact, Yes. During a SELEX experiment, information from the one scientists incorporate and environment is captured in the form of a particular DNA evolution into our discovery efforts is that reality or RNA sequence.27 This information transfer works is often too complex for our attempts at the alterna- because of the relationship between structure and tive: .30 We allow chance and selection information. room to work (in this case, by beginning with a ran- The surface of the target contains information dom oligonucleotide). While SELEX is only twenty about the positions and charges of a huge array of years old as a technique, the idea of the importance electron orbitals (something similar to figure 2c, but of serendipity in science is much older.

236 Perspectives on Science and Christian Faith Jonathan K. Watts

Inthesameway,researchersonboth sides of the biotic selection could act.” “No one knows how early origins debate must recognize that the science of ori- could replicate in the absence of polymerase gins is too complex for our attempts to understand. enzymes.” These statements are currently correct— Indeed, origin-of-life researchers themselves are but rapid progress is being made in both areas.35 often the first to admit that they do not understand It would simply not be true to say, “We know howlifeoriginated.Justbecausewecangenerate that random-sequence oligonucleotides cannot self- biomolecules containing new information in a SELEX assemble” or “We know that enzyme-free RNA repli- experiment does not mean we are anywhere near cation is impossible.” Thus, in spite of his objections understanding or recapitulating the origin of life. to the contrary, Meyer’s arguments about generation of biomolecular information at the origin of life are The ID should also recognize the substantially based on absence of knowledge.36 limits of our knowledge. Biological information is too dynamic to support a law of conservation of information. Hard lines cannot easily be drawn Conclusions between the information in biomolecules and the We must be careful when comparing biological infor- information in the rest of the environment. Substan- mation to familiar forms of information such as text tial shows that biological infor- or computer code. Biological information is not mation increases through natural causes; SELEX abstract; it is intimately tied to the structure and provides one example of such an increase. When function of biomolecules. As such, the biological information is properly understood in its connection information in cells can increase through natural to , it is not surprising that processes. Perhaps the first cell was created out new biological information can arise from natural of nothing—but the high information content of processes. Thus the structural component of biologi- modern cells does not prove this “” cal information adds another of complexity to of the first life. Another option is that processes the origins debate. Biological information is too closely or distantly analogous to SELEX could have complexandtoodynamicforustobeabletomake been used to increase the amount of information in probabilistic claims of a “designed” origin based on a primitive replicating system, although science has the amount of information contained in biological not yet identified such a system. A of wonder systems today. and worship of the Creator is appropriate in either Meyer and Dembski claim that the probabilistic case. resources of the are simply not sufficient As a Christian I believe deeply and thoroughly to allow the generation of information-rich self- in design. But that design does not oppose the fact replicating biomolecules.31 However, an evaluation that both and molecules can accumulate of the of a sequence arising depends information through natural processes. When I read almost entirely on our knowledge of the mechanisms about experiments in molecular evolution, I am whereby such an event may occur.32 For example, often inspired by the complexity and beauty of the Wilf and Ewens have shown that the probability of biomolecules that can generate new information generating a given sequence depends strongly on by interacting with their environment. I am also whether the sequence is independent of history (as in inspired by the creativity of the researchers who did a coin toss) or can preserve advantageous elements not directly design new sequences, but set up a sys- from “ancestor” sequences (as in many types of both tem in which they could measurably evolve. I see SELEX and natural selection).33 unmistakable parallels in ’s activity in the Meyer claims that the argument for direct intelli- world—the beauty and complexity around us gent design of DNA is not based on an absence of speaks of God’s subtlety and majesty, even as there knowledge, but a knowledge of absence.34 Yet, if the is abundant evidence that molecules and organisms ID community responds to the points I have made can generate new information through physical here, they will likely do so using gaps: “No one interactions with their environment. knows how random oligonucleotides could self- It is essential that we avoid the false dichotomy of assemble to provide a starting pool on which pre- “things God did” versus “things science can under-

Volume 63, Number 4, December 2011 237 Article Biological Information, Molecular Structure, and the Origins Debate

stand.” In all of our research, including questions of Novel functions can arise through natural selection, as origins, we should worship God in both the places of shown in Lenski’s long-term evolution experiment; see N. Philippe, L. Pelosi, R. E. Lenski, and D. Schneider, “Evo- our ignorance and of our knowledge. The gaps in lution of Penicillin-Binding Protein 2 Concentration and our knowledge should lead us to greater humility Cell Shape during a Long-Term Experiment with Escherichia and thus worship. Likewise, each new discovery coli,” Journal of Bacteriology 191, no. 3 (2008): 909–21; Z. D. opens our eyes to new depths of beauty in creation, Blount, C. Z. Borland, and R. E. Lenski, “Historical Contin- gency and the Evolution of a Key Innovation in an Experi- and these should also lead us to worship. h mental of ,” Proceedings of the National Academy of Sciences of the USA 105, no. 23 (2008): Notes 7899–906. 1S. Meyer, Signature in the Cell (New York: HarperOne, 2009), For evidence that complex molecular can evolve, chapter 1. see K. Miller, “The Unspun,” http://www 2R. E. Dickerson, H. R. Drew, B. N. Conner, R. M. Wing, .millerandlevine.com/km/evol/design2/article.html. A. V. Fratini, and M. L. Kopka, “The of A-DNA, New information arises through whole-genome duplication B-DNA, and Z-DNA,” Science 216, no. 4545 (1982): 475–85. events and subsequent independent evolution of the two 3J. K. Watts, B. D. Johnston, K. Jayakanthan, A. S. Wahba, copies. See, for example, P. Dehal and J. L. Boore, “Two B. M. Pinto, and M. J. Damha, “Synthesis and Biophysical Rounds of Whole Genome Duplication in the Ancestral Characterization of Oligonucleotides Containing a Vertebrate,” PLoS Biology 3, no. 10 (2005): 1700–8. 4'-Selenonucleotide,” Journal of the American Chemical Society For a perspective on the evolution of information associated 130 (2008): 8578–9. with developmental programs and body plans, see Sean Carroll’s 4L. C. Bock, L. C. Griffin, J. A. Latham, E. H. Vermaas, and J. J. book Endless Forms Most Beautiful (New York: Norton, 2005). Toole, “Selection of Single-Stranded DNA Molecules That 12C. Story, “The God of Christianity and the G.O.D. of Bind and Inhibit Human Thrombin,” Nature 355, no. 6360 ,” Perspectives on Science and Christian Faith 61, (1992): 564–6; C. G. Peng and M. J. Damha, “G-Quadruplex no. 4 (2009): 221–32. Induced Stabilization by 2'-deoxy-2'-fluoro-D-arabino- 13While Meyer does discuss biological evolution to some nucleic Acids (2'F-ANA),” Nucleic Acids Research 35, no. 15 extent in Signature in the Cell, he restricts his version of the (2007): 4977–88. law of conservation of information as follows: “In a nonbio- 5R. F. Macaya, P. Schultze, F. W. Smith, J. A. Roe, and J. logical context, the amount of specified information initially Feigon, “Thrombin-Binding DNA Aptamer Forms a Uni- present in a system, Si, will generally equal or exceed the molecular Quadruplex Structure in Solution,” Proceedings specified information content of the final system, Sf.” See of the National Academy of Sciences of the USA 90, no. 8 Meyer, Signature in the Cell, chapter 13. (1993): 3745–9. 14This is sometimes called “information capacity” or 6Because the four bases have different masses, we can Shannon information. calculate the predicted mass of our desired oligonucleotide. 15Bock, Griffin, Latham, Vermaas, and Toole, “Selection of If the mass is correct, it does not confirm the sequence of Single-Stranded DNA Molecules That Bind and Inhibit the bases, but because of the nature of the chemical syn- Human Thrombin.” The oligonucleotide sequences in thesis cycle, nucleotides are not usually delivered in the the actual experiment were much longer—60 nucleotides incorrect order. If our synthesis fails, it is much more likely of randomized sequence surrounded by 18 nt of known to produce a truncated sequence (i.e., the oligonucleotide sequence on each end (so 96 nt total). The known-sequence missing one or more nucleotides) and will thus be of incor- ends are required for PCR (polymerase chain reaction) rect mass. amplification (the implications of this for information 7R. Isaac, “Information, , and the Origins of Life,” input are discussed later in my article). After five rounds Perspectives on Science and Christian Faith 63, no. 4 (2011): of SELEX, the surviving 96-nt oligonucleotides were 219–30. sequenced, and the researchers observed that a 15-nt motif 8W. A. Dembski, The Design : Eliminating Chance was responsible for the high binding affinity. through Small (New York: Cambridge Univer- 16As a lighter example of SELEX in practice, I could mention sity Press, 1998). that Maureen McKeague won Science magazine’s 2010 9For example, see Meyer, Signature in the Cell, chapter 13. “Dance Your PhD” contest by choreographing the in vitro 10D. R. Venema, “Seeking a Signature,” Perspectives on Science selection of a DNA sequence that binds homocysteine. and Christian Faith 62, no. 4 (2010): 276–83; several responses See http://news.sciencemag.org/sciencenow/2010/10 are available online, including Darrel Falk’s review of the /and-the-dance-your-phd-winner-is.html book at http://biologos.org/blog/signature-in-the-cell and 17Gerald F. Joyce, “Forty Years of in Vitro Evolution,” a multipart series by Dennis Venema beginning at http: Angewandte Chemie International Edition 46, no. 34 (2007): //biologos.org/blog/evolution-and-origin-of-biological 6420–36. -information-part-1-intelligent-design. 18A. D. Ellington and J. W. Szostak, “In Vitro Selection of RNA 11For evidence that natural selection can generate new genes, Molecules That Bind Specific Ligands,” Nature 346, no. 6287 see C. Chandrasekaran and E. Betrán, “Origins of New (1990): 818–22; G. F. Joyce, “Amplification, Mutation and Genes and ,” Nature Education 1, no 1 (2008), Selection of Catalytic RNA,” Gene 82, no. 1 (1989): 83–7; available online at http://www.nature.com/scitable C. Tuerk and L. Gold, “Systematic Evolution of Ligands by /topicpage/origins-of-new-genes-and-pseudogenes-835.

238 Perspectives on Science and Christian Faith Jonathan K. Watts

Exponential Enrichment: RNA Ligands to Bacteriophage T4 31For example, see Meyer, Signature in the Cell, chapter 14. DNA Polymerase,” Science 249, no. 4968 (1990): 505–10. 32J. S. Wilkins and W. R. Elsberry, “The Advantages of Theft 19N. K. Navani and Y. F. Li, “Nucleic Acid Aptamers and over Toil: and Arguing from Enzymes as Sensors,” Current Opinion in 10, Ignorance,” Biology and Philosophy 16, no. 5 (2001): 709–22. no. 3 (2006): 272–81. 33H. S. Wilf and W. J. Ewens, “There’s Plenty of Time for 20E. W. M. Ng, D. T. Shima, P. Calias, E. T. Cunningham, D. R. Evolution,” Proceedings of the National Academy of Sciences of Guyer, and A. P. Adamis, “Pegaptanib, a Targeted Anti- the USA 107, no. 52 (2010): 22454–6. VEGF Aptamer for Ocular Vascular Disease,” Nature 34Meyer, Signature in the Cell, chapter 17. Reviews Discovery 5, no. 2 (2006): 123–32. 35C. Deck, M. Jauker, and C. Richert, “Efficient Enzyme-Free 21See Meyer, Signature in the Cell, chapters 13–14 and Appen- Copying of All Four Templated by Immobi- dix A. These references focus specifically on lized RNA,” Nature Chemistry 3, no. 8 (2011): 603–8; T. A. , a sub-type of SELEX. Lincoln and G. F. Joyce, “Self-Sustained Replication of an 22The oligonucleotides are amplified after each step by the RNA Enzyme,” Science 323, no. 5918 (2009): 1229–32; T. R. polymerase chain reaction (PCR). This famous technique Cech, “The RNA Worlds in Context,” Cold Spring Harbor Per- makes use of a polymerase enzyme that requires a primer to spectives in Biology (2011); P. C. Joshi, M. F. Aldersley, J. W. start the synthesis of each copy it makes. So the wings of Delano, and J. P. Ferris, “Mechanism of Montmorillonite known sequence surrounding our random oligonucleotide Catalysis in the Formation of RNA Oligomers,” Journal of the are primer binding sites (each one is complementary to American Chemical Society 131, no. 37 (2009): 13369–74; M. W. a short primer, and primers must be added during the Powner, B. Gerland, and J. D. Sutherland, “Synthesis of amplification step). In a similar way, DNA sequencing Activated Pyrimidine Ribonucleotides in Prebiotically makes use of a polymerase enzyme and thus requires Plausible Conditions,” Nature 459, no. 7244 (2009): 239–42. a of known sequence. 36Venema has drawn to the particular danger of 23C. Deck, M. Jauker, and C. Richert, “Efficient Enzyme-Free gap-based arguments in a rapidly evolving field of research: Copying of All Four Nucleobases Templated by Immobi- see “, , and Learning from lized RNA,” Nature Chemistry 3, no. 8 (2011): 603–8; T. A. History: A Reply to Meyer,” Perspectives on Science and Lincoln and G. F. Joyce, “Self-Sustained Replication of an Christian Faith 63, no. 3 (2011): 183–92. RNA Enzyme,” Science 323, no. 5918 (2009): 1229–32. 24K. M. Esvelt, J. C. Carlson, and D. R. Liu, “A System for the Continuous of Biomolecules,” Nature ANNOUNCEMENT OF VACANCY 472 (2011): 499–503; M. C. Wright and Gerald F. Joyce, Department of Biology “Continuous in Vitro Evolution of Catalytic Function,” Science 276 (1997): 614–7. Eastern Mennonite University (EMU) invites applicants for 25Calculated as the base 2 of the number of pos- a one-year position in , with the sible states, 420 or 1.1x1012. possibility of its becoming a continuing position. Area 26The interested reader can explore work from researchers of expertise is flexible, but should support the new such as Larry Gold (U. Colorado at Boulder), David Liu MA graduate program in and the under- (Harvard), Gerald Joyce (Scripps), Andy Ellington (U. Texas graduate program in human . Possible areas of at Austin), Yingfu Li (McMaster), (Caltech), expertise that connect to departmental interests include and many others, along with various companies whose , public health, , developmen- focus is generating useful nucleic acid structures by in vitro tal biology, or animal/human anatomy and . evolution and applying them as diagnostic tools, therapeu- The successful applicant will demonstrate effective tics, reagents and so on: SomaLogic, teaching at both introductory and advanced levels. If the position becomes a continuing position, the appli- Aptagen, Archemix, and others. Hundreds of evolved cant will be required to develop a research program functional sequences are indexed and catalogued by the involving undergraduate students, and to participate Ellington lab at http://aptamer.icmb.utexas.edu/. in advising undergraduate and graduate students in 27 The concepts in this section are discussed more fully and in the health sciences. their application to biological evolution in the companion article by Stephen Freeland, “The Evolutionary Origins of Position begins Fall 2012. EMU reserves the right to fill Genetic Information,” Perspectives on Science and Christian the position at any time or to keep the position open. Faith 63, no. 4 (2011): 240–54. Application review begins immediately. Applicants will 28M. W. Kanan, M. M. Rozenman, K. Sakurai, T. M. Snyder, be asked to respond to questions specific to EMU’s and D. R. Liu, “Reaction Discovery Enabled by DNA- mission after the initial inquiry. Send letter of applica- Templated Synthesis and in Vitro Selection,” Nature 431, tion, curriculum vitae, transcripts (unofficial acceptable), no. 7008 (2004): 545–9; M. M. Rozenman, M. W. Kanan, and three reference letters to and D. R. Liu, “Development and Initial Application of Dr. Nancy Heisey a Hybridization-Independent, DNA-Encoded Reaction Dis- Vice President and Undergraduate Academic Dean covery System Compatible with Organic Solvents,” Journal Eastern Mennonite University 1200 Park Road of the American Chemical Society 129 (2007): 14933–8. Harrisonburg, VA 22802 29 Ibid. [email protected] 30 F. H. Arnold, “Design by Directed Evolution,” Accounts of (540) 432-4141 Chemical Research 31 (1998): 125–31. http://www.emu.edu

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