Nucleic acid

Nucleic acids are biological molecules essential for life, and include DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information. Nucleic acids were first discovered by Friedrich Miescher in 1871.^[1] Experimental studies of nucleic acids constitute a major part of modern biological and medical research, and form a foundation for genome and forensic science, as well as the biotechnology and pharmaceutical industries.^[2][3][4]

Occurrence and nomenclature^[5]

The term nucleic acid is the overall name for DNA and RNA, members of a family of biopolymers,^[6] and is synonymous with polynucleotide. Nucleic acids were named for their initial discovery within the nuclueus, and for the presence of phosphate groups (related to phosphoric acid). Although first discovered within the nucleus of eukaryotic cells, nucleic acids are now known to be found in all life forms, including within bacteria, archaea, mitochondria, chloroplasts, viruses and viroids. All living cells and organelles contain both DNA and RNA, while viruses contain either DNA or RNA, but usually not both.^[7] The basic component of biological nucleic acids is the nucleotide, each of which contains a pentose sugar (ribose or deoxyribose), a phosphate group, and a nucleobase. Nucleic acids are also generated within the laboratory, through the use of enzymes^[8] (DNA and RNA polymerases) and by solid-phase chemical synthesis. The chemical methods also enable the generation of altered nucleic acids that are not found in nature,^[9] for example peptide nucleic acids.

Molecular composition and size^[10]

Nucleic acids can vary in size, but are generally very large molecules. Indeed, DNA molecules are probably the largest individual molecules known. Well-studied biological nucleic acid molecules range in size from 21 nucleotides (small interfering RNA) to large chromosomes (human chromosome 1 is a single molecule that contains 247 million base pairs^[11]).

In most cases, naturally occurring DNA molecules are double-stranded and RNA molecules are single-stranded. There are numerous exceptions, however—some viruses have genomes made of double-stranded RNA and other viruses have single-stranded DNA genomes, and, in some circumstances, nucleic acid structures with three or four strands can form.

Nucleic acids are linear polymers (chains) of nucleotides. Each nucleotide consists of three components: a purine or pyrimidine nucleobase (sometimes termed nitrogenous base or simply base), a pentose sugar, and a phosphate group. The substructure consisting of a nucleobase plus sugar is termed a nucleoside. Nucleic acid types differ in the structure of the sugar in their nucleotides - DNA contains 2'-deoxyribose while RNA contains ribose (where the only difference is the presence of a hydroxyl group). Also, the nucleobases found in the two nucleic acid types are different: adenine, cytosine, and guanine are found in both RNA and DNA, while thymine occurs in DNA and uracil occurs in RNA.

The sugars and phosphates in nucleic acids are connected to each other in an alternating chain (sugar-phosphate backbone) through phosphodiester linkages.^[10] In conventional nomenclature, the carbons to which the phosphate groups attach are the 3'-end and the 5'-end carbons of the sugar. This gives nucleic acids directionality, and the ends of nucleic acid molecules are referred to as 5'-end and 3'-end. The nucleobases are joined to the sugars via an N-glycosidic linkage involving a nucleobase ring nitrogen (N-1 for pyrimidines and N-9 for purines) and the 1' carbon of the pentose sugar ring.

Non-standard nucleosides are also found in both RNA and DNA and usually arise from modification of the standard nucleosides within the DNA molecule or the primary (initial) RNA transcript. Transfer RNA (tRNA) molecules contain a particularly large number of modified nucleosides.^[12]

Topology

Double-stranded nucleic acids are made up of complementary sequences, in which extensive Watson-Crick base pairing results in the a highly repeated and quite uniform double-helical three-dimensional structure.^[13] In contrast, single-stranded RNA and DNA molecules are not constrained to a regular double helix, and can adopt highly complex three-dimensional structures that are based on short stretches of intramolecular base-paired sequences that include both Watson-Crick and noncanonical base pairs, as well as a wide range of complex tertiary interactions.^[14]

Nucleic acid molecules are usually unbranched, and may occur as linear and circular molecules. For example, bacterial chromosomes, plasmids, mitochondrial DNA and chloroplast DNA are usually circular double-stranded DNA molecules, while chromosomes of the eukaryotic nucleus are usually linear double-stranded DNA molecules.^[7] Most RNA molecules are linear, single-stranded molecules, but both circular and branched molecules can result from RNA splicing reactions.^[5]

Nucleic acid sequences

Main article: Nucleic acid sequence

One DNA or RNA molecule differs from another primarily in the sequence of nucleotides. Nucleotide sequences are of great importance in biology, since they carry the ultimate instructions that encode all biological molecules, molecular assemblies, subcellular and cellular structures, organs and organisms, and directly enable cognition, memory and behavior (See: Genetics). Enormous efforts have gone into the development of experimental methods to determine the nucleotide sequence of biological DNA and RNA molecules,^[15][16] and today hundreds of millions of nucleotides are sequenced daily at genome centers and smaller laboratories worldwide.

Types of nucleic acids

Deoxyribonucleic acid

Main article: DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms. The main role of DNA molecules is the long-term storage of information and DNA is often compared to a set of blueprints, since it contains the instructions needed to construct other components of cells, such as proteins and RNA molecules. The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in regulating the use of this genetic information.hi

Ribonucleic acid

Main article: RNA

Ribonucleic acid (RNA) functions in converting genetic information from genes into the amino acid sequences of proteins. The three universal types of RNA include transfer RNA (tRNA), messenger RNA (mRNA), and ribosomal RNA (rRNA). Messenger RNA acts to carry genetic sequence information between DNA and ribosomes, directing protein synthesis. Ribosomal RNA is a major component of the ribosome, and catalyzes peptide bond formation. Transfer RNA serves as the carrier molecule for amino acids to be used in protein synthesis, and is responsible for decoding the mRNA. In addition, many other classes of RNA are now known.

Artificial nucleic acid analogs

Main article: Nucleic acid analogues

Artificial nucleic acid analogs have been designed and synthesized by chemists, and include peptide nucleic acid, morpholino- and locked nucleic acid, as well as glycol nucleic acid and threose nucleic acid. Each of these is distinguished from naturally-occurring DNA or RNA by changes to the backbone of the molecule.

See also

• History of biochemistry
• History of molecular biology
• History of RNA biology
• Nucleic acid simulations
• Molecular biology
• Nucleic acid structure
• Nucleic acid methods
• Nucleic acid thermodynamics
• Oligonucleotide synthesis
• Quantification of nucleic acids

References

1. ^ Dahm, R (Jan 2008). "Discovering DNA: Friedrich Miescher and the early years of nucleic acid research". Human genetics 122 (6): 565–81. doi:10.1007/s00439-007-0433-0. ISSN 0340-6717. PMID 17901982. 
2. ^ International Human Genome Sequencing Consortium (2001). "Initial sequencing and analysis of the human genome." (PDF). Nature 409 (6822): 860–921. doi:10.1038/35057062. PMID 11237011. http://www.nature.com/nature/journal/v409/n6822/pdf/409860a0.pdf. 
3. ^ Venter, JC, et al. (2001). "The sequence of the human genome." (PDF). Science 291 (5507): 1304–1351. doi:10.1126/science.1058040. PMID 11181995. http://www.sciencemag.org/cgi/reprint/291/5507/1304.pdf. 
4. ^ Budowle B, van Daal A (April 2009). "Extracting evidence from forensic DNA analyses: future molecular biology directions". BioTechniques 46 (5): 339–40, 342–50. doi:10.2144/000113136. PMID 19480629. 
5. ^ ^{a b} Alberts, Bruce (2008). Molecular biology of the cell. New York: Garland Science. ISBN 0-8153-4105-9. 
6. ^ Elson D (1965). "Metabolism of nucleic acids (macromolecular DNA and RNA)". Annu. Rev. Biochem. 34: 449–86. doi:10.1146/annurev.bi.34.070165.002313. PMID 14321176. 
7. ^ ^{a b} Brock, Thomas D.; Madigan, Michael T. (2009). Brock biology of microorganisms. Pearson / Benjamin Cummings. ISBN 0-321-53615-0. 
8. ^ Mullis, Kary B. The Polymerase Chain Reaction (Nobel Lecture). 1993. (retrieved December 1, 2010) http://nobelprize.org/nobel_prizes/chemistry/laureates/1993/mullis-lecture.html
9. ^ Verma S, Eckstein F (1998). "Modified oligonucleotides: synthesis and strategy for users". Annu. Rev. Biochem. 67: 99–134. doi:10.1146/annurev.biochem.67.1.99. PMID 9759484. 
10. ^ ^{a b} Stryer, Lubert; Berg, Jeremy Mark; Tymoczko, John L. (2007). Biochemistry. San Francisco: W.H. Freeman. ISBN 0-7167-6766-X. 
11. ^ Gregory SG, Barlow KF, McLay KE, et al. (May 2006). "The DNA sequence and biological annotation of human chromosome 1". Nature 441 (7091): 315–21. doi:10.1038/nature04727. PMID 16710414. 
12. ^ Rich A, RajBhandary UL (1976). "Transfer RNA: molecular structure, sequence, and properties". Annu. Rev. Biochem. 45: 805–60. doi:10.1146/annurev.bi.45.070176.004105. PMID 60910. 
13. ^ Watson JD, Crick FH (April 1953). "Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid". Nature 171 (4356): 737–8. Bibcode 1953Natur.171..737W. doi:10.1038/171737a0. PMID 13054692. 
14. ^ Ferré-D'Amaré AR, Doudna JA (1999). "RNA folds: insights from recent crystal structures". Annu Rev Biophys Biomol Struct 28: 57–73. doi:10.1146/annurev.biophys.28.1.57. PMID 10410795. 
15. ^ Gilbert, Walter G. 1980. DNA Sequencing and Gene Structure (Nobel Lecture) http://nobelprize.org/nobel_prizes/chemistry/laureates/1980/gilbert-lecture.html
16. ^ Sanger, Frederick. 1980. Determination of Nucleotide Sequences in DNA (Nobel Lecture) http://nobelprize.org/nobel_prizes/chemistry/laureates/1980/sanger-lecture.html

Further reading

• Wolfram Saenger, Principles of Nucleic Acid Structure, 1984, Springer-Verlag New York Inc.
• Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter Molecular Biology of the Cell, 2007, ISBN 978-0-8153-4105-5. Fourth edition is available online through the NCBI Bookshelf: link
• Jeremy M Berg, John L Tymoczko, and Lubert Stryer, Biochemistry 5th edition, 2002, W H Freeman. Available online through the NCBI Bookshelf: link

External links

• Interview with Aaron Klug, Nobel Laureate for structural elucidation of biologically important nucleic-acid protein complexes provided by the Vega Science Trust.
• Nucleic Acids Research (Journal)