Nucleic Acids

Nucleic Acids (DNA and RNA)

Nucleic acids (DNA and RNA) are biopolymers, macromolecules that carry genetic information and participate in protein synthesis. Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are the two classes of nucleic acids for all known forms of life. They are long-chain polymers composed of nucleotides. These nucleotides are the monomer components that contain a sugar unit, a phosphate group, and a nitrogenous base. When the sugar unit is ribose, the polymer is RNA but if the sugar unit is deoxyribose, the polymer is DNA.

The sugars and phosphates in nucleic acids are connected to each other in an alternating chain to form a sugar-phosphate backbone through phosphodiester linkages.

Discovery of Nucleic Acid

Nucleic acid was first discovered in 1869 by Swiss biochemist Friedrich Miescher and was given its first name, nuclein. He gave its first name nuclein because he had isolated it from the nucleus of white blood cells.

The compound that was isolated was neither a protein nor a lipid or carbohydrate. Therefore, it was a unique type of biomolecule.

In the early 1880s, Albrecht Kossel purified the substance and identified its acidic properties. A few years later, he also explored the chemistry of nuclein and identified the nucleobases found in nuclein. It contains organic bases adenine, thymine, guanine, and cytosine.

The term nucleic acid was first used by Richard Altmann at a time when DNA and RNA were not differentiated. In 1889, he removed the proteins from the nuclein found in yeast cells and named the remaining material nucleic acid.

In about 1910, it was not realized that there were two types of nucleic acid (DNA and RNA) found in living organisms. Modern research on nucleic acid stepped forward when James Watson and Francis Crick proposed the double helix structure of DNA in 1953. This type of research on nucleic acid constitutes a major part of modern biochemistry, genome forensic science, and medical research.

Types of Nucleic Acids

Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are the two most important types of nucleic acids found in all living cells. These nucleic acids play a key factor in transferring genetic information from one generation to the next generation.

Deoxyribonucleic Acid (DNA)

Like other biomolecules (RNA and proteins, carbohydrates), DNA is one of the most important biopolymers or macromolecules that are essential for all known forms of life.

Deoxyribonucleic acid (DNA) is one of the most important nucleic acids that contains the genetic instructions for the development and functioning of all known living organisms. The DNA segments that carry genetic information in living organisms are called genes. The sequences in the nucleic acid DNA uses for regulating this genetic information.

Structure of DNA Molecule

DNA is a biopolymer that made up of monomeric units, called nucleotides. A nucleotide of such nucleic acid contains a 5-carbon sugar (deoxyribose), a nitrogenous base, and one or more phosphate groups.

The building blocks of nucleotide consist of three phosphate groups. However, during DNA synthesis, two are lost. Therefore, the DNA strand contains one phosphate group per nucleotide.

DNA molecules consist of four different bases. These are double-ring heterocyclic purine bases (adenine and guanine) and single-ring pyrimidine bases (cytosine and thymine).

Each monomer of deoxyribose has a phosphate group linked to the 5′ carbon atom. The nitrogenous base is linked to the 1′ carbon atom by N-glyosidic bonding.

Ribonucleic Acid (RNA)

Ribonucleic acid (RNA) is another important class of nucleic acid that is chemically similar to deoxyribonucleic acid (DNA). It carries genetic information from genes into the amino acid sequences during protein synthesis.

It is a polymer of ribonucleotides held together by 3, 5-phosphodiester bridges. The ribonucleotides in RNA molecules contain 5-carbon sugar ribose, a phosphate, and a nitrogenous base.

Although nucleic acid RNA has certain similarities with the DNA structure, they also have specific differences. The most common differences between DNA and RNA structure are

1. The sugar in RNA is ribose but the sugar in DNA structure is deoxyribose.
2. RNA contains the pyrimidine base uracil in place of thymine.
3. RNA is usually a single-stranded polynucleotide but DNA has a double-stranded structure.
4. Due to the single-stranded nature, there is no specific relation between purine and pyrimidine bases.

Types of RNA

Messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA) are the three major types of RNAs found in the cell and functioning during protein biosynthesis.

Besides these three RNAs, other RNAs are also present in the cells. These RNAs are

• Heterogeneous nuclear RNA (hnRNA)
• Small nuclear RNA (snRNA)
• Small nucleolar RNA (snoRNA)
• Small cytoplasmic RNA (scRNA)

These various types of RNAs are synthesized from DNA molecules. They primarily involved in the process of protein biosynthesis. They are very similar in their structure and biological functions.

• Messenger RNA (mRNA): It transfers genetic information from genes to ribosomes during protein biosynthesis.
• Transfer RNA (tRNA): Transfers an amino acid to mRNA for making protein biomolecules for living organisms.
• Ribosomal RNA (rRNA): It provides the structural framework for ribosomes.
• Heterogeneous nuclear RNA (hnRNA): A precursor for mRNA.
• Small nuclear RNA (snRNA): Involved in mRNA processing.
• Small nucleolar RNA (snoRNA): It plays a key role in processing rRNA molecules.

Artificial Nucleic Acids

Artificial nucleic acids are structurally similar to naturally occurring RNA and DNA. The most common artificial nucleic acids are peptide nucleic acid (PNA), glycol nucleic acid (GNA), threose nucleic acid (TNA), and hexitol nucleic acids (HNA).

These artificial nucleic acids differ from natural DNA and RNA by changes in the backbone of the molecule. Xeno nucleic acids (XNA) are artificial analogs that consist solely of synthetic nucleotide monomers but the chemical composition of the sugar moiety has been changed. They are important to investigate possible scenarios of the origin of life.

Nucleic Acid Sequence

A nucleic acid sequence is a succession of nitrogenous bases (pyrimidines and purines) within the nucleotides. One DNA or RNA molecule differs from another DNA or RNA molecule primarily on the basis of the sequence of nucleotides.

The letters A, C, G, and T represent the four nucleotide bases (adenine, cytosine, guanine, and thiamine) of a DNA strand. They are covalently linked to a phosphodiester backbone.

One sequence is complementary to another sequence. For example, the complementary sequence of TTAC is GTAA. Hence, the bases in each position are complementary ( A = T, C = G) but reverse in order.

A gene is a linear nucleotide sequence of a DNA molecule containing the information required to synthesize a macromolecule having a specific cellular function. The determination of nucleotide sequence in a DNA molecule is the basic and fundamental requirement of biotechnology. Therefore, millions of nucleotides of nucleic acids are sequenced daily at genome centers and smaller laboratories or test centers.

DNA sequencing is important to understand the functions of genes and the diagnosis and treatment of diseases. The accurate knowledge of DNA sequences is also useful for DNA cloning and gene manipulation.

Structure of Nucleic Acids

Nucleic acids (DNA and RNA) are the vital constituents of living organisms. They are long-chain polymers of nucleotides (polynucleotides) held by 3’ and 5’-phosphate bridges. Without an attached phosphate group, the sugar unit attached to one of the bases is called a nucleoside.

Nucleotides are basic building blocks or monomeric units of nucleic acids. Besides these, nucleotides also perform various biological activities in living organisms,

• Purine and pyrimidine nucleotides can control various biological activities such as energy metabolism, protein synthesis, and controlling enzyme activities.
• Nucleotides are the structural components of some coenzymes (FAD, NAD) of the B vitamins.
• Sugar derivatives of nucleotides, namely UDP-glucose, participate in the synthesis of glycogen.
• In medical science, various synthetic analogs of nucleotides uses in the treatment of cancer, AIDS, and the induction of an immune response during organ transplantation.

Bases in Nucleic Acids

Purines and pyrimidines are two major types of nitrogenous bases found in nucleic acid (DNA and RNA) structures. The nitrogenous bases found in nucleic acids (DNA and RNA) are aromatic heterocyclic compounds.

DNA and RNA contain the same purine bases namely adenine (A) and guanine (G). However, the pyrimidine base cytosine is found in both DNA and RNA molecules.

The nucleic acid differs with respect to the second pyrimidine base. DNA contains thymine (T), whereas RNA contains uracil (U) in its structure. The structures of thymine and uracil differ by the presence or absence of the methyl group.

Sugars in Nucleic Acids

The five-carbon organic monosaccharides (pentoses) are found in the nucleic acid structure. RNA contains D-ribose while DNA contains D-deoxyribose in its structure.

The pentose sugar in DNA differs from the sugar of RNA by the absence of a hydroxyl group (―OH) present on the 2′ carbon of the sugar unit. Therefore, ribose and deoxyribose differ in structure at the C₂ position. Deoxyribose in DNA has one oxygen less at C2 compared to ribose in RNA.

Nucleic Acid Synthesis

During normal cell metabolism, RNA is constantly being made and broken down but purine and pyrimidine residues are reused by several salvage pathways to make more genetic material.

Nucleotides in DNA and RNA are synthesized from readily available materials found in the cell. All nucleotides found in living organisms contain a sugar, a phosphate, and a nitrogenous base. The ribose phosphate portion of nucleotides in nucleic acid synthesized from glucose via the pentose phosphate pathway.

The six-membered heterocyclic pyrimidine ring is synthesized first and subsequently attached to the ribose phosphate. The two heterocyclic purine rings are also synthesized and attached to the ribose phosphate during the assembly of adenine or guanine nucleosides.

RNA Synthesis

A specialized enzyme, a kinase can add two phosphate groups from adenosine triphosphate (ATP) to form ribonucleoside triphosphate from ribonucleoside phosphate. The ribonucleoside triphosphate is an immediate precursor of RNA.

DNA Synthesis

The 2′-hydroxyl group is removed from the ribonucleoside diphosphate to form deoxyribonucleoside diphosphate. Deoxyribonucleoside triphosphate (an immediate precursor of DNA) is formed by the addition of another phosphate group from ATP by the enzyme kinase.

Function of Nucleic Acids

Two nucleic acids such as deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are found in living things that store, translate, and pass the genetic information from one generation to the next generation.

They are universal to all forms of life and found in the nucleus of eukaryotic and prokaryotic cells, and various viruses. The mitochondria of eukaryotic cells also contain some type of DNA. It is called mitochondrial DNA (mDNA).

Nucleic acids are large biomolecules that play various essential biological functions in living cells. The major biological functions of nucleic acids are

• Nucleic acids store and express genomic information in living organisms.
• Nucleic acids (DNA and RNA) are the main information-carrying molecules of the cell which direct the process of protein synthesis.
• DNA is the chemical basis of heredity and it may be regarded as the reserve bank of genetic information.
• DNA is extensively responsible for maintaining the identities of different species of organisms over millions of years.
• The nucleic acid DNA is organized into genes, the fundamental units of genetic information. The genes in nucleic acids are important in encoding the information for making proteins in living organisms.

Nucleic Acids in Cells

Now, nucleic acids known to be found in all forms of life including within bacteria, archaea, mitochondria, chloroplasts, and viruses. Most living cells contain both DNA and RNA while viruses contain either DNA or RNA.

Nucleic acids are also generated within the laboratory by the action of enzyme DNA and RNA polymerases.

Nucleic acids (DNA and RNA) form by repeated synthesis reactions between nucleotides that contain a sugar unit, a phosphate group, and a nitrogenous base.

They linked to each other by a phosphodiester linkage between the phosphate group of one nucleotide and the sugar unit of another nucleotide.

Importance of Nucleic Acids

Nucleic acids are large biomolecules that play various essential roles in cells of living organisms. The storage and expression of genomic information is a major function of nucleic acids.

The nucleotides in nucleic acid (DNA) carry genetic information which reads by cells to make RNA and proteins by which living things function.

Nucleic Acids and Proteins

Nucleic acid, deoxyribonucleic acid (DNA), encodes the information in cells to synthesize proteins in living organisms.

A related type of nucleic acid, called ribonucleic acid (RNA) can also play an important role in protein synthesis. These two nucleic acids determine the structural sequence of amino acids and the biological functions of the protein.

Messenger RNA (mRNA) is a nucleic acid that is translated to make a protein. During translation, a messenger RNA can read the information in a cell and use it to build a protein.