The nucleic acids DNA and RNA are key macromolecules in the continuity of life. They carry the genetic blueprint of a cell and carry instructions for the functioning of the cell. DNA is the genetic material passed from parent to offspring for all life on Earth. With the exception of identical twins, each person’s DNA is unique and it is possible to detect differences between human beings on the basis of their unique DNA sequence. In addition, the DNA macromolecule has a species-specific structure due to the aperiodic ordering of the nitrogenous bases in its structure. RNA is mostly involved in protein synthesis and its regulation. The DNA molecules never leave the nucleus, but instead use an RNA intermediary to communicate with the rest of the cell.
The structure of nucleic acids DNA and RNA
Nucleic acids are macromolecular chemicals that represent the longest polymers in the living world.
The structure of DNA
The model of the deoxyribonucleic acid (DNA) macromolecule was proposed by Watson and Crick. The building blocks of DNA are nucleotides; hence the DNA molecule is a polymer of nucleotides. Each nucleotide is made up of three parts: a nitrogenous base, a pentose (a monosaccharide with five-carbon atoms) and a phosphate group. The pentose in DNA is deoxyribose and the phosphate group is a residue of phosphoric acid, which is an inorganic compound.
There are four types of nitrogenous bases in a DNA nucleotide: adenine (A) and guanine (G) are double-ringed purines and cytosine (C) and thymine (T) are smaller, single-ringed pyrimidines (Figure 5.1). A nucleotide is named according to the nitrogenous base it contains. The phosphate group of one nucleotide bonds covalently with the sugar molecule of the next nucleotide, and so on, forming a long polymer of nucleotide monomers. The sugar-phosphate groups line up in a “backbone” for each single strand of DNA, and the nucleotide bases stick out from this backbone. The carbon atoms of the five-carbon sugar are numbered clockwise from the oxygen as 1′, 2′, 3′, 4′, and 5′ (1′ is read as “one prime”). The phosphate group is attached to the 5′ carbon of one nucleotide and the 3′ carbon of the next nucleotide.
Figure 5.1: The purines have a double ring structure with a six-member ring fused to a five-member ring. Pyrimidines are smaller in size; they have a single six-member ring structure.
Watson and Crick proposed that the DNA is made up of two strands that are twisted around each other to form a right handed helix, called a double helix. Base-pairing takes place between a purine and pyrimidine: namely, A pairs with T, and G pairs with C. In other words, adenine and thymine are complementary base pairs, and cytosine and guanine are also complementary base pairs. This is the basis for Chargaff’s rule: because of their complementarity, there is as much adenine as thymine in a DNA molecule and as much guanine as cytosine.
Adenine and thymine are connected by two hydrogen bonds and cytosine and guanine are connected by three hydrogen bonds. The two strands are anti-parallel in nature; that is, one strand will have the 3′ carbon of the sugar in the “upward” position, whereas the other strand will have the 5′ carbon in the upward position. The diameter of the DNA double helix is uniform throughout because a purine (two rings) always pairs with a pyrimidine (one ring) and their combined lengths are always equal (Figure 5.2).
Figure 5.2: DNA has (a) a double helix structure and (b) phosphodiester bonds; the dotted lines between Thymine and Adenine respective Guanine and Cytosine represent hydrogen bonds. (c) The major and minor grooves are sites for DNA binding proteins during processes such as transcription and replication.
The eukaryotic cell has two types of DNA: nuclear and mitochondrial.
- Nuclear DNA is the genetic material contained in the cell nucleus.
In the nucleus of diploid somatic cells (containing pairs of homologous chromosomes), regardless of tissue, the content in DNA is approximately equal. In the nucleus of haploid gamete cells (with unpaired chromosomes), the amount of DNA is reduced by half. The amount of DNA is directly proportional to the number of chromosomes, diploid or haploid, and is dependent on the phases of the cell cycle. - Mitochondrial DNA is the genetic material of mitochondria, cellular organs with redox function involved in cellular respiration. This type of DNA is responsible for the synthesis of respiratory enzymes.
The structure of RNA
Like DNA, the ribonucleic acid (RNA) is a polymer of nucleotides. Each of the nucleotides in RNA is made up of a nitrogenous base, a pentose (a monosaccharide with five-carbon atoms) and a phosphate group. The pentose in RNA is ribose and the phosphate group is a residue of phosphoric acid. Ribose has a hydroxyl group at the 2′ carbon, unlike deoxyribose, which has only a hydrogen atom (Figure 5.3).
Figure 5.3: The difference between the ribose found in RNA and the deoxyribose found in DNA is that ribose has a hydroxyl group at the 2′ carbon, unlike deoxyribose, which has only a hydrogen atom.
RNA nucleotides contain the nitrogenous bases adenine, cytosine, and guanine. However, they do not contain thymine, which is instead replaced by uracil, symbolized by a “U.” RNA exists as a single-stranded molecule rather than a double stranded helix.
Molecular biologists have named several kinds of major RNA macromolecules on the basis of their function. These include:
- messenger RNA (mRNA) – serves as a template for protein synthesis;
- transfer RNA (tRNA) – transports amino acids to the site of protein synthesis;
- ribosomal RNA (rRNA) – is a major constituent of ribosomes, cellular structures in which protein synthesis is performed.
Distribution of nucleic acids in the cell
RNA makes up about 5-10% of the cell mass and DNA only about 1%.
The two types of DNA in a cell have different proportions: a large amount is represented by nuclear DNA (97-99%) and only a small amount (1-3%) by mitochondrial DNA.
The three types of major RNA in a cell have different proportions: a large amount is represented by rRNA (80-90% of cellular RNA), a small amount by tRNA (a proportion of 10-15%) and a very small amount by mRNA (less than 5%).
Figure 5.4: RNA versus DNA.
How DNA is arranged in the cell
DNA is a working molecule; it must be replicated when a cell is ready to divide, and it must be “read” to produce the molecules, such as proteins, to carry out the functions of the cell. For this reason, the DNA is protected and packaged in very specific ways. In addition, DNA molecules can be very long. Stretched end-to-end, the DNA molecules in a single human cell would come to a length of about 2 meters. Thus, the DNA for a cell must be packaged in a very ordered way to fit and function within a structure (the cell) that is not visible to the naked eye.
Figure 5.5: Eukaryotes contain a well-defined nucleus that hosts several chromosomes, while prokaryotes have a single chromosome that lies in an area of the cytoplasm called nucleoid.
The chromosomes of prokaryotes are much simpler than those of eukaryotes in many of their features. Most prokaryotes contain a single, circular chromosome that is found in an area in the cytoplasm called nucleoid (Figure 5.5). The size of the genome in one of the most well-studied prokaryotes, Escherichia coli, is 4.6 million base pairs, which would extend a distance of about 1.6 mm if stretched out. So how does this fit inside a small bacterial cell? The DNA is twisted beyond the double helix in what is known as supercoiling. Some proteins are known to be involved in the supercoiling; other proteins and enzymes help in maintaining the supercoiled structure.
Eukaryotes, whose chromosomes each consist of a linear DNA macromolecule, employ a different type of packing strategy to fit their DNA inside the nucleus (Figure 5.6). At the most basic level, DNA is wrapped around the proteins known as histones to form the structures called nucleosomes. The DNA is wrapped tightly around the histone core. A nucleosome is linked to the next one by a short strand of DNA that is free of histones. This structure is also known as the “beads on a string” structure: the nucleosomes are the “beads” and the short lengths of DNA between them are the “string.” The nucleosomes, with their DNA coiled around them, stack compactly onto each other to form a 30-nm–wide fiber. This fiber is further coiled into a thicker and more compact structure.
At the metaphase stage of mitosis, when the chromosomes are lined up in the center of the cell, the chromosomes are at their most compacted. They are approximately 700 nm in width, and are found in association with the scaffold proteins. In interphase, the phase of the cell cycle between mitoses at which the chromosomes are decondensed, eukaryotic chromosomes have two distinct regions that can be distinguished by staining. There is a tightly packaged region that stains darkly and a less dense region. The darkly staining regions usually contain genes that are not active and are found in the regions of the centromere and telomeres. The lightly staining regions usually contain genes that are active, with DNA packaged around nucleosomes but not further compacted.
Figure 5.6: The compaction of the eukaryotic chromosome.
Functions of nucleic acids
DNA biochemically encodes genetic information in the form of a specific sequence of nitrogenous bases that can self-reproduce and be transferred by transcription to mRNA molecules, based on the principle of complementarity of nitrogenous bases. The genetic message carried by mRNA is translated at the level of ribosomes, the centers of protein synthesis.
The two functions performed by nucleic acids are:
- The autocatalytic function is how DNA reproduces itself.
- The heterocatalytic function is how DNA controls the development of the body – how it conveys its genetic information to the rest of the body.
References:
- Fowler, Samantha, et al. Concepts of Biology. OpenStax College, Rice University, 2013. Download for free at: https://openstax.org/details/books/concepts-biology.