Nucleic acid

Nucleic acids are large biomolecules essential to all cells and viruses. They are built from smaller units called nucleotides, each made of a five-carbon sugar, a phosphate group, and a nitrogenous base. The two major types are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). When the sugar is ribose, the molecule is RNA; when it is deoxyribose—a modified form of ribose—the molecule is DNA. These compounds occur naturally and serve as the carriers of genetic information, encoding and storing instructions within every living cell of every life-form on Earth. They also transmit and express that information both inside and outside the cell nucleus, guiding protein synthesis through the specific sequence of nucleotides, which gives DNA and RNA their characteristic ladder-like order of base pairs.

Nucleotides link together to form spiral backbones, assembling into chains of bases selected from five primary nucleobases: adenine, cytosine, guanine, thymine, and uracil. Thymine is found only in DNA, and uracil only in RNA. RNA typically forms a single-stranded chain, while DNA forms a double-stranded chain of base pairs. The precise sequence of these base pairs in DNA stores and transmits coded instructions as genes, and in RNA, the base-pair sequence helps produce proteins that drive most chemical processes in all life forms.

Historically, nucleic acid was first partially discovered by Friedrich Miescher in 1869 at the University of Tübingen, Germany. He identified a substance he called nuclein, which modern interpretation views as either a nucleic acid-histone complex or the nucleic acid itself. Phoebus Levene later determined the basic structure of nucleic acids. In the early 1880s, Albrecht Kossel further purified the substance, noted its strong acidic properties, and identified the nucleobases. In 1889, Richard Altmann coined the term nucleic acid, at a time when DNA and RNA were not yet distinguished. In 1938, Astbury and Bell published the first X-ray diffraction pattern of DNA. The Avery–MacLeod–McCarty experiment in 1944 demonstrated that DNA carries genetic information, and in 1953, Watson and Crick proposed the double-helix structure of DNA. Experimental studies of nucleic acids are now central to modern biological and medical research, forming the basis of genomics, forensic science, and the biotechnology and pharmaceutical industries.

The term nucleic acid encompasses both DNA and RNA, which are biopolymers and types of polynucleotides. They were named for their initial discovery in the cell nucleus and for the presence of phosphate groups, which are related to phosphoric acid. Although first found in the nucleus of eukaryotic cells, nucleic acids are now known to occur in all life forms, including bacteria, archaea, mitochondria, chloroplasts, and viruses (though whether viruses are living is debated). All living cells contain both DNA and RNA, except some cells like mature red blood cells, while viruses contain either DNA or RNA, but usually not both. The basic component of biological nucleic acids is the nucleotide, each containing a pentose sugar (ribose or deoxyribose), a phosphate group, and a nucleobase. Nucleic acids can also be synthesized in the lab using enzymes (DNA and RNA polymerases) or solid-phase chemical synthesis.

Nucleic acids are generally very large molecules; DNA molecules are among the largest individual molecules known. Well-studied biological nucleic acids range in size from 21 nucleotides (small interfering RNA) to large chromosomes, such as human chromosome 1, which is a single molecule containing 247 million base pairs. Most naturally occurring DNA is double-stranded, and most RNA is single-stranded, but there are exceptions: some viruses have double-stranded RNA genomes, others have single-stranded DNA genomes, and in certain conditions, three- or four-stranded structures can form. Nucleic acids are linear polymers of nucleotides. Each nucleotide has three components: a purine or pyrimidine nucleobase, a pentose sugar, and a phosphate group that makes the molecule acidic. The combination of a nucleobase and sugar is called a nucleoside. The two nucleic acid types differ in their sugar: DNA contains 2'-deoxyribose, while RNA contains ribose, the only difference being the presence of a hydroxyl group. The nucleobases also differ: adenine, cytosine, and guanine occur in both, but thymine is unique to DNA and uracil to RNA. The sugars and phosphates form an alternating chain (sugar-phosphate backbone) linked by phosphodiester bonds. The carbons where phosphate groups attach are the 3'-end and 5'-end carbons, giving nucleic acids directionality; the ends are referred to as 5'-end and 3'-end. Nucleobases attach to the sugar via an N-glycosidic linkage, involving a ring nitrogen (N-1 for pyrimidines, N-9 for purines) and the 1' carbon of the pentose sugar. Non-standard nucleosides also occur in both types.