Nucleic acid

Nucleic acidsRNA(left) andDNA(right).

Nucleic acidsare largebiomoleculesthat are crucial in all cells and viruses.They are composed ofnucleotides,which are themonomercomponents: a5-carbon sugar,aphosphate groupand anitrogenous base.The two main classes of nucleic acids aredeoxyribonucleic acid(DNA) andribonucleic acid(RNA). If thesugarisribose,thepolymeris RNA; if the sugar isdeoxyribose,a variant of ribose, the polymer is DNA.

Nucleic acids are chemical compounds that are found in nature. They carry information in cells and make up genetic material. These acids are very common in all living things, where they create, encode, and store information in every living cell of everylife-formon Earth. In turn, they send and express that information inside and outside the cell nucleus. From the inner workings of the cell to the young of a living thing, they contain and provide information via thenucleic acid sequence.This gives the RNA and DNA their unmistakable 'ladder-step' order of nucleotides within their molecules. Both play a crucial role in directingprotein synthesis.

Strings of nucleotides are bonded to form spiraling backbones and assembled into chains of bases or base-pairs selected from the fiveprimary, or canonical, nucleobases.RNA usually forms a chain of single bases, whereas DNA forms a chain of base pairs. The bases found in RNA and DNA are:adenine,cytosine,guanine,thymine,anduracil.Thymine occurs only in DNA and uracil only in RNA. Usingamino acidsandprotein synthesis,the specific sequence in DNA of thesenucleobase-pairshelps to keep and sendcodedinstructions asgenes.In RNA, base-pair sequencing helps to make new proteins that determine most chemical processes of all life forms.

History

TheSwissscientistFriedrich Miescherdiscovered the "nuclein", in 1868. Later, he raised the idea that it could be involved inheredity.

Nucleic acid was, partially, first discovered byFriedrich Miescherin 1869 at theUniversity of Tübingen,Germany. He discovered a new substance, which he callednucleinand which - depending on how his results are interpreted in detail - can be seen in modern terms either as a nucleid acid-histoncomplex or as the actual nucleid acid.Phoeber Aaron Theodor Levene, an American biochemist determined the basic structure of nucleic acids.In the early 1880s,Albrecht Kosselfurther purified the nucleid acid substance and discovered its highly acidic properties. He later also identified thenucleobases. In 1889Richard Altmanncreated the term nucleic acid – at that time DNA and RNA were not differentiated. In 1938Astburyand Bell published the first X-ray diffraction pattern of DNA.

In 1944 theAvery–MacLeod–McCarty experimentshowed that DNA is the carrier of genetic information and in 1953WatsonandCrickproposed the double-helix structure of DNA.

Experimental studies of nucleic acids constitute a major part of modernbiologicalandmedical research,and form a foundation forgenomeandforensic science,and thebiotechnologyandpharmaceutical industries.

Occurrence and nomenclature

The termnucleic acidis the overall name for DNA and RNA, members of a family ofbiopolymers,and is a type ofpolynucleotide.Nucleic acids were named for their initial discovery within thenucleus,and for the presence of phosphate groups (related to phosphoric acid).Although first discovered within thenucleusofeukaryoticcells, nucleic acids are now known to be found in all life forms including withinbacteria,archaea,mitochondria,chloroplasts,andviruses(There is debate as towhether viruses are living or non-living). All living cells contain both DNA and RNA (except some cells such as mature red blood cells), while viruses contain either DNA or RNA, but usually not both. The basic component of biological nucleic acids is thenucleotide,each of which contains apentose sugar(riboseordeoxyribose), aphosphategroup, and anucleobase. Nucleic acids are also generated within the laboratory, through the use ofenzymes(DNA and RNA polymerases) and bysolid-phase chemical synthesis.

Molecular composition and size

Nucleic acids 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 1is a single molecule that contains 247 millionbase pairs).

In most cases, naturally occurring DNA molecules aredouble-strandedand RNA molecules are single-stranded.There are numerous exceptions, however—some viruses have genomes made ofdouble-stranded RNAand other viruses havesingle-stranded DNAgenomes,and, in some circumstances, nucleic acid structures withthreeorfourstrands can form.

Nucleic acids are linearpolymers(chains) of nucleotides. Each nucleotide consists of three components: apurineorpyrimidinenucleobase(sometimes termednitrogenous baseor simplybase), apentosesugar,and aphosphategroup which makes the molecule acidic. The substructure consisting of a nucleobase plus sugar is termed anucleoside.Nucleic acid types differ in the structure of the sugar in their nucleotides–DNA contains 2'-deoxyribosewhile RNA containsribose(where the only difference is the presence of ahydroxyl group). Also, the nucleobases found in the two nucleic acid types are different:adenine,cytosine,andguanineare found in both RNA and DNA, whilethymineoccurs in DNA anduraciloccurs in RNA.

The sugars and phosphates in nucleic acids are connected to each other in an alternating chain (sugar-phosphate backbone) throughphosphodiesterlinkages.Inconventional nomenclature,the carbons to which the phosphate groups attach are the 3'-end and the 5'-end carbons of the sugar. This gives nucleic acidsdirectionality,and the ends of nucleic acid molecules are referred to as 5'-end and 3'-end. The nucleobases are joined to the sugars via anN-glycosidic linkage involving a nucleobase ring nitrogen (N-1 for pyrimidines andN-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.

Topology

Double-stranded nucleic acids are made up of complementary sequences, in which extensiveWatson-Crick base pairingresults in a highly repeated and quite uniform nucleic aciddouble-helicalthree-dimensional structure.In contrast, single-stranded RNA and DNA molecules are not constrained to a regular double helix, and can adopthighly complex three-dimensional structuresthat are based on short stretches of intramolecular base-paired sequences including both Watson-Crick and noncanonical base pairs, and a wide range of complex tertiary interactions.

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.Most RNA molecules are linear, single-stranded molecules, but both circular and branched molecules can result fromRNA splicingreactions.The total amount of pyrimidines in a double-stranded DNA molecule is equal to the total amount of purines. The diameter of the helix is about 20Å.

Sequences

Main article:Nucleic acid sequence

Further information:Genetics

One DNA or RNA molecule differs from another primarily in thesequence 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. Enormous efforts have gone into the development of experimental methods to determine the nucleotide sequence of biological DNA and RNA molecules,and today hundreds of millions of nucleotides aresequenceddaily at genome centers and smaller laboratories worldwide. In addition to maintaining the GenBank nucleic acid sequence database, theNational Center for Biotechnology Information(NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI web site.

Types

Deoxyribonucleic acid

Main article:DNA

Deoxyribonucleic acid (DNA) is a nucleic acid containing the genetic instructions used in the development and functioning of all known living organisms. The chemical DNA was discovered in 1869, but its role in genetic inheritance was not demonstrated until 1943. The DNA segments that carry this genetic information are called genes. Other DNA sequences have structural purposes, or are involved in regulating the use of this genetic information. Along with RNA and proteins, DNA is one of the three major macromolecules that are essential for all known forms of life. DNA consists of two long polymers ofmonomerunits called nucleotides, with backbones made of sugars and phosphate groups joined by ester bonds. These two strands are oriented in opposite directions to each other and are, therefore,antiparallel.Attached to each sugar is one of four types of molecules called nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes genetic information. This information specifies the sequence of the amino acids within proteins according to thegenetic code.The code is read by copying stretches of DNA into the related nucleic acid RNA in a process called transcription. Within cells, DNA is organized into long sequences called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes. Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA in organelles, such as mitochondria or chloroplasts. In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm. Within the chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

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 RNAacts to carry genetic sequence information between DNA and ribosomes, directing protein synthesis and carries instructions from DNA in the nucleus to ribosome.Ribosomal RNAreads the DNA sequence, and catalyzes peptide bond formation.Transfer RNAserves as the carrier molecule for amino acids to be used in protein synthesis, and is responsible for decoding the mRNA. In addition, many otherclasses of RNAare now known.

Artificial nucleic acid

Main article:Nucleic acid analogue

Artificialnucleic acid analogueshave been designed and synthesized.They includepeptide nucleic acid,morpholino- andlocked nucleic acid,glycol nucleic acid,andthreose nucleic acid.Each of these is distinguished from naturally occurring DNA or RNA by changes to the backbone of the molecules.

See also

• Comparison of nucleic acid simulation software
• History of biochemistry
• History of molecular biology
• History of RNA biology
• Molecular biology– Branch of biology that studies biological systems at the molecular level is called molecular biology
• Nucleic acid methods– Techniques used to study nucleic acids
• Nucleic acid metabolism– ProcessPages displaying short descriptions with no spaces
• Nucleic acid structure– Biomolecular structure of nucleic acids such as DNA and RNA
• Nucleic acid thermodynamics– Study of how temperature affects the nucleic acid structure
• Oligonucleotide synthesis– Chemical synthesis of relatively short fragments of nucleic acids with defined chemical structure
• Quantification of nucleic acids– commonly performed to determine the average concentrations of DNA or RNA present in a mixture, as well as their purityPages displaying wikidata descriptions as a fallback

Bibliography

• 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 WalterMolecular Biology of the Cell,2007,ISBN978-0-8153-4105-5.Fourth edition is available online through the NCBI Bookshelf:link
• Jeremy M Berg, John L Tymoczko, and Lubert Stryer,Biochemistry5th edition, 2002, W H Freeman. Available online through the NCBI Bookshelf:link
• Astrid Sigel; Helmut Sigel; Roland K. O. Sigel, eds. (2012).Interplay between Metal Ions and Nucleic Acids.Metal Ions in Life Sciences. Vol. 10. Springer.doi:10.1007/978-94-007-2172-2.ISBN978-94-007-2171-5.S2CID92951134.

Further reading

• Palou-Mir J, Barceló-Oliver M, Sigel RK (2017). "Chapter 12. The Role of Lead(II) in Nucleic Acids". In Astrid S, Helmut S, Sigel RK (eds.).Lead: Its Effects on Environment and Health.Metal Ions in Life Sciences. Vol. 17. de Gruyter. pp. 403–434.doi:10.1515/9783110434330-012.PMID28731305.

External links

• Interview with Aaron Klug, Nobel Laureate for structural elucidation of biologically important nucleic-acid protein complexesprovided by the Vega Science Trust.
• Nucleic Acids Researchjournal
• Nucleic Acids Book (free online book on the chemistry and biology of nucleic acids)
• Visualization of nucleotide sequence