Genetic Alphabet Research Articles

Primordial coding of amino acids by adsorbed purine bases.

Scanning tunneling microscopy and chromatography experiments exploring the potential templating properties of nucleic acid bases adsorbed to the surface of crystalline graphite, revealed that the interactions of amino acids with the bare crystal surface are significantly modulated by the prior adsorption of adenine and hypoxanthine. These bases are the coding elements of a putative purine-only genetic alphabet and the observed effects are different for each of the bases. Such mapping between bases and amino acids provides a coding mechanism. These observations demonstrate that a simple pre-RNA amino acid discrimination mechanism could have existed on the prebiotic Earth providing critical functionality for the origin of life.

Efforts toward creating unnatural base pairs for an expanded genetic code.

A series of unnatural base pairs was designed and examined for the expansion of the genetic alphabet and for a better understanding of the mechanism of nucleic acid biosyntheses. To improve the shape complementarity of the previously developed unnatural base pairs, 2-amino-6-(N,N-dimethylamino)purine (x)--pyridon-2-one (y) and 2-amino-6-(2-thienyl)purine (s)--y, the pyrimidine analogue, y, was replaced by a five-member ring, 4-imidazolin-2-one (z), and the s-z pairing in replication was examined. Unnatural bases based on the five-member ring were also applied to the development of non-hydrogen-bonded base pairs.

Efforts toward expansion of the genetic alphabet: replication of DNA with three base pairs.

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTEfforts toward Expansion of the Genetic Alphabet: Replication of DNA with Three Base PairsEunju Lee Tae, Yiqin Wu, Gang Xia, Peter G. Schultz, and Floyd E. RomesbergView Author Information Department of Chemistry The Scripps Research Institute 10550 North Torrey Pines Road La Jolla, California 92037 Cite this: J. Am. Chem. Soc. 2001, 123, 30, 7439–7440Publication Date (Web):July 4, 2001Publication History Received21 March 2001Published online4 July 2001Published inissue 1 August 2001https://doi.org/10.1021/ja010731eCopyright © 2001 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views737Altmetric-Citations75LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (49 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:DNA replication,Genetics,Kinetics,Nucleic acids,Peptides and proteins Get e-Alerts

A Novel Copper-Mediated DNA Base Pair

DNA encodes information in the sequence of the four deoxynucleotides dA, dT, dG, and dC. The key element for information storage and retrieval in this four-letter alphabet involves selective hydrogen bonding in the complementary base pairs dA:dT and dG:dC. Are these universal bases a unique structural solution for the genetic code, or are there other base pairing schemes that can be incorporated into DNA? To address this question, we and others have begun to synthesize and evaluate base pairs with alternate pairing interactions. The ability to generate additional such pairs would not only increase the capacity of DNA for information storage 1 but would also allow the replication of DNA containing novel functional groups. 2 In addition, nucleic acids completely built out of artificial base pairs could lead to novel polymers with interesting chemical and physical properties. Efforts to expand the genetic alphabet have focused largely on two strategies: hydrogen bonding patterns different from those in dA:dT and dG:dC 3 and hydrophobic packing interactions. 4,5 Here we describe a new strategy which is based on the metaldependent pairing of two nucleobases. 6,7 We have designed a base

Efforts toward Expansion of the Genetic Alphabet: Optimization of Interbase Hydrophobic Interactions

Six novel unnatural nucleobases have been characterized that form stable base pairs in duplex DNA, relying not on hydrogen bonds, but rather on interbase hydrophobic interactions. These nucleobases are derivatives of the hydrophobic base pair between 7-azaindole (7AI) and isocarbostyril (ICS). Derivatives of 7AI and ICS were examined that have increased hydrophobic surface area, as well as increased polarizability. As observed with 7AI and ICS, these derivatives are recognized as substrates by Klenow fragment of Escherichia coli DNA polymerase I. The unnatural base pair between pyrrolopyrizine (PP) and C3-methylisocarbostyril (MICS) is enzymatically incorporated into DNA with high efficiency (kcat/KM = 106 M-1 min-1) and moderate selectivity. These studies represent a significant step toward the generation of a stable, orthogonal base pair that can be enzymatically incorporated into DNA with good fidelity.

Efforts toward the Expansion of the Genetic Alphabet: Information Storage and Replication with Unnatural Hydrophobic Base Pairs

The faithful recognition of the interstrand hydrogen bonds between complementary nucleobases forms the foundation of the genetic code. The ability to replicate DNA containing a stable third base pair would allow for an expansion of the information content of DNA by supplementing the existing two base pairs of the genetic alphabet with a third. We report the optimization of unnatural nucleobases whose pairing in duplex DNA is based on interbase hydrophobic interactions. We show that the stability and selectivity of such unnatural base pairs may be comparable to, or even exceed, that of native pairs. We also demonstrate that several unnatural base pairs are incorporated into DNA by Klenow fragment of Escherichia coli DNA polymerase I with an efficiency equivalent to that of native DNA synthesis. Moreover, the unnatural bases are orthogonal to the native bases, with correct pairing being favored by at least an order of magnitude relative to mispairing.

Efforts toward Expansion of the Genetic Alphabet: DNA Polymerase Recognition of a Highly Stable, Self-Pairing Hydrophobic Base

The storage and replication of biological information is based on the specific hydrogen-bonding patterns of the Watson-Crick A:T and G:C base pairs.1 The generation of enzymatically replicable unnatural base pairs with thermal stability comparable to that of A:T and G:C would significantly expand the biological and chemical potential of DNA. One strategy for expanding the genetic alphabet has focused on the synthesis of bases with altered hydrogen-bonding patterns.2-8 However, in light of the dominant role played by hydrophobicity in protein folding and stability,9-11 we have explored the use of hydrophobic and van der Waals interactions to generate an orthogonal base pair for the storage and replication of genetic information. Previous experiments in which hydrophobic bases were incorporated into duplex DNA led to a destabilization of the duplex relative to the native pairs.12-18 In the course of systematically evaluating a variety of predominantly hydrophobic nucleobases,19 we have characterized a base, which cannot form H-bonds, whose self-pair stabilizes duplex DNA relative to an A:T or G:C base pair. The 7-propynyl isocarbostyril nucleoside (1) was synthesized and converted into the nucleoside triphosphate (4) and phosphoramidite (5) as shown in Scheme 1. When incorporated into duplex DNA, the 1:1 interstrand interaction is expected to be completely hydrophobic in the absence of significant backbone deformation; the keto groups are designed to be in the minor groove and can H-bond to solvent. The thermal stability of the base pairs was evaluated by determining the melting temperature (Tm) of the duplex 7 with X,Y ) G:C, A:T, or 1:1 (Table 1). The 1:1 hydrophobic base pair stabilizes the DNA duplex relative to

Synthesis of 2′-Deoxyisoguanosine 5′-Triphosphate and 2′-Deoxy-5-methylisocytidine 5′-Triphosphate

The syntheses of the 5′-triphosphates of 2′-deoxyisoguanosine (=p3isoGd) and 2′-deoxy-5-methylisocytidine (=p3me5isoCd), two new bases for the genetic alphabet, are described. The triphosphates were synthesized from the corresponding nucleosides using a transient-protection procedure. The introduction of a methyl group at the 5-position of 2′-deoxyisocytidine remarkably improved the stability of the triphosphate. Characterization of the triphosphates included enzymatic incorporation opposite the complementary base in a template oligonucleotide.

Recognition of a non-standard base pair by thermostable DNA polymerases.

Examination of several commercially available thermostable DNA polymerases identifies 9 degrees N DNA polymerase as single enzyme that could incorporate two components of an expanded genetic alphabet, 2,4-diaminopyrimidine and xanthosine as deoxynucleoside triphosphate opposite their cognate base in a DNA template.

A code in the protein coding genes

A statistical analysis with 12 288 autocorrelation functions applied in protein (coding) genes of prokaryotes and eukaryotes identifies three subsets of trinucleotides in their three frames: T 0= X 0∪{AAA, TTT} with X 0={AAC, AAT, ACC, ATC, ATT, CAG, CTC, CTG, GAA, GAC, GAG, GAT, GCC, GGC, GGT, GTA, GTC, GTT, TAC, TTC} in frame 0 (the reading frame established by the ATG start trinucleotide), T 1= X 1∪{CCC} in frame 1 and T 2= X 2∪{GGG} in frame 2 (the frames 1 and 2 being the frame 0 shifted by one and two nucleotides, respectively, to the right). These three subsets are identical in these two gene populations and have five important properties: (i) the property of maximal (20 trinucleotides) circular code for X 0 (resp. X 1, X 2) allowing to retrieve automatically the frame 0 (resp. 1, 2) in any region of the gene without start codon; (ii) the DNA complementarity property C (e.g. C (AAC)=GTT): C ( T 0)= T 0, C ( T 1)= T 2 and C ( T 2)= T 1 allowing the two paired reading frames of a DNA double helix simultaneously to code for amino acids; (iii) the circular permutation property P (e.g. P (AAC)=ACA): P ( X 0)= X 1 and P ( X 1)= X 2 implying that the two subsets X 1 and X 2 can be deduced from X 0; (iv) the rarity property with an occurrence probability of X 0=6×10 −8; and (v) the concatenation properties in favour of an evolutionary code: a high frequency (27.5%) of misplaced trinucleotides in the shifted frames, a maximum (13 nucleotides) length of the minimal window to retrieve automatically the frame and an occurrence of the four types of nucleotides in the three trinucleotide sites. In Discussion, a simulation based on an independent mixing of the trinucleotides of T 0 allows to retrieve the two subsets T 1 and T 2. Then, the identified subsets T 0, T 1 and T 2 replaced in the 2-letter genetic alphabet {R, Y} (R=purine=A or G, Y=pyrimidine=C or T) allow to retrieve the RNY model (N=R or Y) and to explain previous works in the alphabet {R, Y}. Then, these three subsets are related to the genetic code. The trinucleotides of T 0 code for 13 amino acids: Ala, Asn, Asp, Gln, Glu, Gly, Ile, Leu, Lys, Phe, Thr, Tyr and Val. Finally, a strong correlation between the usage of the trinucleotides of T 0 in protein genes and the amino acid frequencies in proteins is observed as six among seven amino acids not coded by T 0, have as expected the lowest frequencies in proteins of both prokaryotes and eukaryotes.

Synthesis and Characterization of Non‐standard Nucleosides and Nucleotides Bearing the Acceptor‐Donor‐Donor Pyrimidine Analog 6‐Amino‐3‐methylpyrazin‐2(1H)‐one

Abstract6‐Aminopyrazin‐2(1H)‐one, when incorporated as a pyrimidine‐base analog into an oligonucleotide chain, presents a H‐bond acceptor‐donor‐donor pattern to a complementary purine analog. When paired with the corresponding donor‐acceptor‐acceptor purine in oligonucleotides, the heterocycle selectively contributes to the stability of the duplex, presumably by forming a base pair of Watson‐Crick geometry joined by a non‐standard H‐bonding pattern. Aspects of the nucleoside chemistry, including syntheses of the β‐furanosyl ribonucleoside 1, the ribonucleoside triphosphate 2 and the ribonucleoside bisphosphate 3 of 6‐aminopyrazin‐2(1H)‐one are reported here. In aqueous solution, the ribonucleoside 1 was found to undergo acid‐ and base‐catalyzed rearrangement with an apparent half‐life of ca. 63 h at neutral pH and 30°. The rearrangement appears to be specific acid‐ and base‐catalyzed. The thermodynamically most stable compound formed during this rearrangement reaction was isolated by HPLC and shown to be the β‐pyranosyl form 4 of the 6‐aminopyrazin‐2(1H)‐one nucleoside in its 4C1 chair conformation. This reactivity of 1 under physiological conditions may explain why Nature does not use this particular heterocyclic system to implement an acceptor‐donor‐donor H‐bonding pattern in the genetic alphabet.

Synthesis, Molecular Recognition, and Enzymology of Oligonucleotides Containing the Non‐standard Base Pair between 5‐Aza‐7‐deazaisoguanine and 6‐Amino‐3‐methylpyrazin‐2(1H)‐one, a Donor‐Acceptor‐Acceptor Purine Analog and an Acceptor‐Donor‐Donor Pyrimidine Analog

AbstractA 6‐aminopyrazin‐2(1H)‐one (pyADD), when incorporated as a pyrimidine‐base analog into an oligonucleotide chain, presents a H‐bond acceptor‐donor‐donor pattern to 5‐aza‐7‐deazaisoguanine (puDAA), the complementrary donor‐acceptor‐acceptor purine analog. Reported here are the syntheses of the phosphoramidite of the 2′‐deoxyribonucleoside bearing the puDAA base, oligonucleotides containing this nucleoside unit, the enzyme‐assisted synthesis of oligoribonucleotides containing the pyADD ribonucleoside, and the molecular‐recognition properties of this non‐standard base pair in an oligonucleotide context. A series of melting experiments suggests that the pyADD · puDAA base pair contributes to the relative stability of a duplex structure approximately the same as an A · T base pair, and significantly more than mismatches between these non‐standard bases and certain standard nucleobases. The pyADD nucleoside bisphosphate is accepted by T4 RNA ligase, but the triphosphate of the pyADD nucleoside was not incorported by T7 RNA polymerase opposite the puDAA nucleobase in a template. Oligonucleotides containing the pyADD base slowly undergo a reversible first‐order reaction, presumably an epimerization process to give the α‐D‐anomer. These experiments provide the tools for laboratory‐based use of the pyADD · puDAA base pair as a component of an oligonucleotide‐like molecular‐recognition system based on an expanded genetic alphabet.

A Complementary Circular Code in the Protein Coding Genes

Recently, shifted periodicities 1 modulo 3 and 2 modulo 3 have been identified in protein (coding) genes of both prokaryotes and eukaryotes with autocorrelation functions analysing eight of 64 trinucleotides (Arquès et al., 1995). This observation suggests that the trinucleotides are associated with frames in protein genes. In order to verify this hypothesis, a distribution of the 64 trinucleotides AAA,...,TTT is studied in both gene populations by using a simple method based on the trinucleotide frequencies per frame. In protein genes, the trinucleotides can be read in three frames: the reading frame 0 established by the ATG start trinucleotide and frame 1 (resp. 2) which is the frame 0 shifted by 1 (resp. 2) nucleotide in the 5′–3′ direction. Then, the occurrence frequencies of the 64 trinucleotides are computed in the three frames. By classifying each of the 64 trinucleotides in its preferential occurrence frame, i.e. the frame associated with its highest frequency, three subsets of trinucleotides can be identified in the three frames. This approach is applied in the two gene populations. Unexpectedly, the same three subsets of trinucleotides are identified in these two gene populations: T 0= X 0∪ {AAA,TTT} with X 0= {AAC,AAT,ACC,ATC,ATT,CAG,CTC,CTG,GAA,GAC,GAG,GAT,GCC,GGC,GGT,GTA,GTC,GTT,TAC,TTC} in frame 0, T 1= X 1∪ {CCC} in frame 1 and T 2= X 2∪ {GGG} in frame 2, each subset X 0, X 1and X 2having 20 trinucleotides. Surprisingly, these three subsets have five important properties: (i) the property of maximal circular code for X 0(resp. X 1, X 2) allowing the automatical retrieval of frame 0 (resp. 1, 2) in any region of a protein gene model (formed by a series of trinucleotides of X 0) without using a start codon; (ii) the DNA complementarity property C(e.g. C(AAC) = GTT): C( T 0) = T 0, C( T 1) = T 2and C( T 2) = T 1allowing the two paired reading frames of a DNA double helix simultaneously to code for amino acids; (iii) the circular permutation property P(e.g. P(AAC) = ACA); P( X 0) = and P( X 1) = X 2implying that the two subsets X 1and X 2can be deduced from X 0; (iv) the rarity property with an occurrence probability of X 0equal to 6 × 10 −8; and (v) the concatenation property with: a high frequency (27.5%) of misplaced trinucleotides in the shifted frames, a maximum (13 nucleotides) length of the minimal window to automatically retrieve the frame and an occurrence of the four types of nucleotides in the three trinucleotides sites, in favour of an evolutionary code. In the Discussion, the identified subsets T 0, T 1and T 2replaced in the three two-letter genetic alphabets purine/pyrimidine, amino/ceto and strong/weak interaction, allow us to deduce that the RNY model (R = purine = A or G, Y = pyrimidine = C or T, N = R or Y) (Eigen & Schuster, 1978) is the closest two-letter codon model to the trinucleotides of T 0. Then, these three subsets are related to the genetic code. The trinucleotides of T 0code for 13 amino acids: Ala, Asn, Asp, Gln, Glu, Gly, Ile, Leu, Lys, Phe, Thr, Tyr, and Val. Finally, a strong correlation between the usage of the trinucleotides of T 0in protein genes and the amino acid frequencies in proteins is observed as six among seven amino acids not coded by T 0have as expected the lowest frequencies in proteins of both prokaryotes and eukaryotes.

Differential discrimination of DNA polymerase for variants of the non-standard nucleobase pair between xanthosine and 2,4-diaminopyrimidine, two components of an expanded genetic alphabet.

Mammalian DNA polymerases alpha and epsilon, the Klenow fragment of Escherichia coli DNA polymerase I and HIV-1 reverse transcriptase (RT) were examined for their ability to incorporate components of an expanded genetic alphabet in different forms. Experiments were performed with templates containing 2'-deoxyxanthosine (dX) or 2'-deoxy-7-deazaxanthosine (c7dX), both able to adopt a hydrogen bonding acceptor-donor-acceptor pattern on a purine nucleus (puADA). Thus these heterocycles are able to form a non-standard nucleobase pair with 2,4-diaminopyrimidine (pyDAD) that fits the Watson-Crick geometry, but is joined by a non-standard hydrogen bonding pattern. HIV-1 RT incorporated d(pyDAD)TP opposite dX with a high efficiency that was largely independent of pH. Specific incorporation opposite c7dX was significantly lower and also independent of pH. Mammalian DNA polymerases alpha and epsilon from calf thymus and the Klenow fragment from E. coli DNA polymerase I failed to incorporate d(pyDAD)TP opposite c7dX.

Theoretical investigation of the molecular structure of the pi kappa DNA base pair.

The structure of the nonclassical pi kappa base pair (7-methyl-oxoformycin B. . .2,4-diaminopyrimidine) was studied at the ab initio Hartree-Fock (HF) and MP2 levels using the 6-31G* and 6-31G** basis sets. The pi kappa base pair is bound by three parallel hydrogen bonds with the donor-acceptor-donor recognition pattern. Recently, these bases were proposed as an extension of the genetic alphabet from four to six letters (Piccirilli et al, Nature 343,33 (1990)). By the HF/6-31G* method with full geometry optimization we calculated the 12 degree propeller twist for the minimum energy structure of this complex. The linearity of hydrogen bonds is preserved in the twisted structure by virtue of the pyramidal arrangement of the kappa-base amino groups. The rings of both the pi and kappa molecules remain nearly planar. This nonplanar structure of the pi kappa base pair is only 0.1 kcal/mol more stable than the planar (Cs) conformation. The HF/6-31G* level gas-phase interaction energy of pi kappa (-13.5 kcal/mol) calculated by us turned out to be nearly the same as the interaction energy obtained previously for the adenine-thymine base pair (-13.4 kcal/mol) at the same computational level. The inclusion of p-polarization functions on hydrogens, electron correlation effects (MP2/6-31G** level), and the correction for the basis set superposition error (BSSE) increase this energy to -14.0 kcal/mol.

Peptide nucleic acid (PNA) conformation and polymorphism in PNA-DNA and PNA-RNA hybrids.

Two hydrogen-bonding motifs have been proposed to account for the extraordinary stability of polyamide "peptide" nucleic acid (PNA) hybrids with nucleic acids. These interresidue- and intraresidue-hydrogen-bond motifs were investigated by molecular mechanics calculations. Energy-minimized structures of Watson-Crick base-paired decameric duplexes of PNA with A-, B-, and Z-DNA and A-RNA polymorphs indicate that the inherent stability of the complementary PNA helical structures is derived from interresidue, rather than from intraresidue, hydrogen bonds in all hybrids studied. Intraresidue-hydrogen-bond lengths are consistently longer than interresidue hydrogen bonds. Helical strand stability with interresidue hydrogen bond stabilization follows the order: B-(DNA.PNA) > A-(DNA.PNA) congruent to A-RNA.PNA > Z-(DNA.PNA). In the triplex hybrids A-(RNA.PNA2) and B-(DNA.PNA2), differences between stabilities of the two decamers of thyminyl PNA with lysine amide attached to the C terminus (pnaT)10 strands are small. The Hoogsteen (pnaT)10 strands are of slightly higher potential energy than are the Watson-Crick (pnaT)10 strands. Antiparallel arrangement of PNAs in the triplex is slightly favored over the parallel arrangement based on the calculations. Examination by molecular mechanics of the PNA.DNA analogue of the NMR-derived structure for the B-double-stranded DNA dodecamer d(CG-CAAATTTGCG)2 in solution suggests that use of all bases of the genetic alphabet should be possible without loss of the specific interresidue-hydrogen-bonding pattern within the PNA strand.

What is the optimum size for the genetic alphabet?

An important question in biology is why the genetic alphabet is made of just two base pairs (G.C and A.T). This is particularly interesting because of the recent demonstration [Piccirilli, J. A., Krauch, T., Moroney, S. E. & Benner, S. A. (1990) Nature (London) 343, 33-37] that the alphabet can in principle be larger. It is possible to explain the size of the present genetic alphabet as a frozen character state that was an evolutionary optimum in an RNA world when nucleic acids functioned both for storing genetic information and for expressing information as enzymatically active RNA molecules--i.e., ribozymes. A previous model [Szathmáry, E. (1991) Proc. R. Soc. London Ser. B 245, 91-99] has described the principle of this approach. The present paper confirms and extends these results by showing explicitly the ways in which copying fidelity and metabolic efficiency change with the size of the genetic alphabet.

A C-nucleotide base pair: methylpseudouridine-directed incorporation of formycin triphosphate into RNA catalyzed by T7 RNA polymerase

With templates containing 2'-deoxy-1-methylpseudouridine (dm psi), T7 RNA polymerase catalyzes the incorporation of either adenosine triphosphate (ATP) or formycin triphosphate (FTP) into a growing chain of RNA with the same efficiency as with templates containing thymidine (dT). In each case, the overall rate of synthesis of full-length products containing formycin is about one-tenth of the rate of synthesis of analogous products containing adenosine. Analysis of the products of abortive initiation shows that incorporation of FMP into the growing oligonucleotide by T7 RNA polymerase is more likely to lead to premature termination of transcription than is incorporation of AMP. Nevertheless, the results demonstrate that T7 RNA polymerase tolerates the formation of a C-nucleotide transcription complex in which the nucleoside bases on both the template and the incoming nucleotide are joined to the ribose by a carbon-carbon bond. This result increases the prospects for further expanding the genetic alphabet via incorporation of new base pairs with novel hydrogen-bonding schemes (Piccirilli et al., 1990).

Four letters in the genetic alphabet: a frozen evolutionary optimum?

Piccirilli et al. (Nature, Lond. 343, 33-37 (1990)) have shown experimentally that the replicatable introduction of new base pairs into the genetic alphabet is chemically feasible. The fact that our current genetic alphabet uses only two base pairs can be explained provided that this basic feature of organisms became fixed in an RNA world utilizing ribozymes rather than protein enzymes. The fitness of such ribo-organisms is determined by two factors: replication fidelity and overall catalytic efficiency (basic metabolic or growth rate). Replication fidelity is shown to decrease roughly exponentially, and catalytic efficiency is shown to increase with diminishing returns, with the number of letters for a fixed genome length; hence their product, i.e. fitness, gives rise to a set of values with an optimum. Under a wide range of parameter values the optimum rests at two base pairs. The chemical identity of the particular choice in our genetic alphabet can also be rationalized. This optimum is considered frozen, as currently the dominant catalysts are proteins rather than RNAs.

Genetic alphabet for RNA gains two letters

Researchers in Switzerland have added two letters to the genetic alphabet, opening the possibility of synthesizing new types of RNA with greater catalytic potential. The genetic alphabet used by RNA molecules consists of only four letters, or bases: the purines adenine (A) and guanine (G), and the pyrimidines cytosine (C) and uracil (U). In double-stranded RNA, these bases, arranged along a sugar-phosphate backbone, hydrogen-bond to a complementary chain of bases so that each adenine is paired with a uracil and each guanine is paired with a cytosine. DNA differs from RNA only in that uracil is replaced by another pyrimidine, thymine (T), and the backbone sugar is deoxyribose instead of ribose. Thus, nature relies on only two types of base pairs (A-U or A-T, and G-C) to carry genetic information. But other types of base pairs are possible, as biological chemist Steven A. Benner and associates at the Swiss Federal Institute of Technology in Zurich have ...