Nucleic acid

Nucleic acids are large biomolecules present in all living cells and viruses. They function as the primary carriers of genetic information, enabling organisms to store, transmit, and express the instructions required for growth, reproduction, and cellular regulation. Structurally, they are polymers composed of repeating nucleotide units, each containing a pentose sugar, a phosphate group, and a nitrogenous base. The two principal types are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), distinguished mainly by their sugar components and by the presence of thymine in DNA and uracil in RNA.
Nucleic acids form the molecular basis of heredity and protein synthesis. DNA typically appears as a double-stranded helix made of complementary base pairs, whereas RNA is usually single-stranded, capable of folding into diverse functional structures. Through their nucleotide sequences, nucleic acids encode the genetic code that underpins all biological processes.

Composition and structural features

The basic building block of nucleic acids is the nucleotide, composed of a nitrogenous base (a purine or pyrimidine), a pentose sugar, and a phosphate group. Bases include adenine, cytosine, guanine, thymine, and uracil. Adenine pairs with thymine in DNA and with uracil in RNA, while guanine pairs with cytosine in both types. The sugar–phosphate backbone of nucleic acids forms through phosphodiester linkages between the 3′ and 5′ carbon atoms of neighbouring sugars, giving each polymer a directional 5′ to 3′ structure.
A nucleotide lacking the phosphate group is termed a nucleoside. Variations in structure also occur through modified nucleosides, particularly abundant in transfer RNA, where chemical alterations enhance stability and functional complexity.
DNA generally forms a uniform double helix, with complementary sequences producing predictable base-pairing patterns. In contrast, single-stranded RNA can adopt complex secondary and tertiary structures based on internal base-pairing, non-canonical interactions, and three-dimensional folding. Unusual structures such as triple-stranded DNA, circular RNA, and G-quadruplex arrangements can occur in specific biological contexts. The size of nucleic acid molecules varies greatly, from short regulatory RNAs comprising a few dozen nucleotides to large chromosomes containing millions of base pairs.

Discovery and historical development

The history of nucleic acids spans more than a century of scientific investigation. The Swiss scientist Friedrich Miescher first identified a phosphorus-rich substance he termed “nuclein” in 1869 while studying cell nuclei. Although he did not determine its full significance, his discovery laid the foundation for later work.
By the 1880s Albrecht Kossel had purified the substance further and identified the major nucleobases, recognising its acidic properties. Richard Altmann introduced the term “nucleic acid” in 1889. In the early twentieth century Phoebus Levene elucidated the general structure of nucleotides, identifying their sugar, base, and phosphate components.
Advances in X-ray crystallography in the 1930s included the first diffraction images of DNA, providing insights into its repeating structure. The 1944 Avery–MacLeod–McCarty experiment demonstrated that DNA, rather than protein, carries hereditary information. This realisation culminated in 1953 when James Watson and Francis Crick proposed the double-helical model of DNA, drawing upon structural studies and base-ratio evidence.
Technological progress in the late twentieth century, including the development of polymerase chain reaction and DNA sequencing methods, further transformed molecular biology. These breakthroughs now underpin modern genomics, forensic science, biotechnology, and biomedical research.

Occurrence and biological roles

Although named for their initial isolation from the eukaryotic cell nucleus, nucleic acids are found in all forms of life, including bacteria, archaea, and even organelles such as mitochondria and chloroplasts. Viruses contain either DNA or RNA as their genetic material, but generally not both simultaneously. Most living cells carry both types, with rare exceptions such as mature mammalian red blood cells, which lack nuclei and genetic material.
The primary function of nucleic acids is to encode biological information. DNA stores the long-term genetic blueprint, while various forms of RNA carry out a wide range of roles, including transcription, translation, and regulation. Messenger RNA relays genetic instructions, ribosomal RNA forms structural and catalytic components of ribosomes, and transfer RNA delivers amino acids during protein synthesis. Regulatory RNAs, including small interfering RNA and microRNA, modulate gene expression.
Nucleic acids can also be synthesised artificially. Enzymatic polymerases allow controlled replication of nucleic acid sequences, while chemical solid-phase synthesis enables the laboratory creation of specific DNA or RNA fragments used in research, diagnostics, and therapeutics.

Molecular size, configuration, and topology

Nucleic acid molecules vary dramatically in length and structural arrangement. DNA molecules are often among the largest known biological polymers; for instance, human chromosome 1 comprises approximately 247 million base pairs. DNA in eukaryotes generally occurs as linear double-stranded molecules, while bacterial chromosomes, plasmids, and organellar genomes are typically circular.
RNA molecules are usually single-stranded, although branched or circular forms can arise during processing events. Secondary structural elements such as hairpins and loops form through intramolecular complementarity. Both RNA and DNA may exhibit alternative configurations under certain conditions, such as supercoiling or triple-helix formation.
In double-stranded DNA the total number of purines equals the total number of pyrimidines, reflecting consistent base-pairing. The average diameter of the helix is about 20 Å, a key factor in its stability and regularity.

Nucleotide sequences and biological information

The linear sequence of nucleotides within DNA or RNA is the fundamental determinant of biological specificity. These sequences encode the instructions for constructing proteins, guiding cellular architecture, and regulating physiological processes. Consequently, methods for determining nucleotide sequences revolutionised biology. Pioneering sequencing techniques developed in the late 1970s enabled researchers to read genetic information directly, launching the era of genomics.
Today, genome centres and laboratories worldwide sequence billions of nucleotides, contributing to extensive public databases. Resources developed by international organisations facilitate analysis, comparison, and retrieval of nucleic acid data across species and experimental contexts.

Types and functions of DNA and RNA

Deoxyribonucleic acid (DNA) serves as the repository of hereditary information for virtually all known organisms. Although discovered in the nineteenth century, its role in inheritance was confirmed only in the 1940s. Genes are DNA segments that encode functional products, principally proteins.
Ribonucleic acid (RNA) carries out a wider array of roles. Beyond its involvement in transcription and translation, RNA participates in regulation, catalysis, viral replication, and epigenetic control. Its single-stranded nature permits structural versatility, enabling functions that extend well beyond genetic messaging.