GENETICS - Textbook - A.V. Sivolob - 2008

CHAPTER 1. The Nature of Genetic Material

As a physical object, a Gene is a segment of a polymer molecule known as deoxyribonucleic acid (DNA). The only exception to this rule, which applies to All living organisms, is a specific Class of Viruses where information is carried by another nucleic acid (a chemical analogue of DNA)—ribonucleic acid (RNA). Numerous types of RNA also play an essential role in the expression of Genetic information across all organisms.

The PHYSICOCHEMICAL PROPERTIES OF the DNA molecule make it a reliable repository for hereditary information and provide a simple mechanism for Replication—the precise duplication of the molecule (and, consequently, the hereditary program) in daughter Cells during Cell Division. The numerous interactions of DNA with other molecules (primarily Proteins) determine its specific packaging pattern within cells, the expression of genetic information and its regulation, as well as other processes vital to the functioning of The hereditary apparatus.

DNA STRUCTURE

Chemical Structure of Nucleic Acids

The monomeric unit of a nucleic acid—the nucleotide—consists of three components: a nitrogenous base, a pentose sugar (ribose or deoxyribose), and a phosphoric acid residue (Fig. 1.1).

Fig. 1.1. Chemical Structure of a nucleotide.

The standard numbering of pentose ring atoms is shown

Fig. 1.2. Nitrogenous bases. The N atom bonded to the C1' atom of the pentose in the nucleotide is highlighted in red. The standard numbering of purine and pyrimidine ring atoms is shown

Nitrogenous bases are heterocyclic compounds (Fig. 1.2) containing carbon and nitrogen in their rings, with all bonds possessing partial double-bond character. Exocyclic groups, such as an amino group or an oxygen atom, are attached to specific ring atoms. Nucleic Acids contain Two Types of nitrogenous bases: Purines (commonly designated as R)—adenine (A)

and guanine (G); Pyrimidines (Y)—uracil (U), thymine (T), and cytosine (C). The general designation for all bases is N. Within a nucleotide, one of the ring nitrogen atoms (highlighted in red in Fig. 1.2) is linked by a covalent bond to the carbon of the pentose sugar (Fig. 1.1). This pentose atom is designated as C1' (the prime symbol ' is used to distinguish the atoms of the pentose ring from those of the nitrogenous base). The remaining C' atoms of the pentose are numbered sequentially in the order of their arrangement (Fig. 1.1). An OH group is always attached to the 3'-carbon. A pentose that also bears an OH group at the 2'-position is called ribose. Another type of pentose found in nucleic acids—deoxyribose—differs only by the replacement of this OH group with a hydrogen atom.

A compound formed by a nitrogenous base and a pentose is called a nucleoside (depending on the type of nitrogenous base: adenosine, guanosine, cytidine, thymidine, uridine) or a ribo- or deoxyribonucleoside (depending on the type of pentose). Ribonucleosides are constituents of RNA, whereas deoxyribonucleosides form part of DNA. Another chemical distinction between DNA and RNAS concerns the composition of pyrimidine nitrogenous bases: T is present in DNA instead of U in RNA.

Phosphorylation of the OH group at the 5'-carbon of the pentose in a nucleoside leads to The formation of a nucleotide (Fig. 1.1). Thus, a nucleotide is a nucleoside phosphate or nucleoside monophosphate (NMP). For instance, the nucleotide shown in Fig. 1.1 is adenosine monophosphate (AMP).

The building blocks for the synthesis of polymeric nucleic acids are nucleoside triphosphates, which contain two additional phosphate groups sequentially attached to the 5'-phosphate; these are cleaved during synthesis reactions.

During synthesis, two chemical groups—the OH group at the 3'-carbon of one nucleotide and the phosphate at the 5'-carbon of another—are utilized to form a phosphodiester bond between the NUCLEOTIDES (Fig. 1.3). Consequently, a polynucleotide chain has a directionality: one end terminates in a 5'-phosphate (the 5'-end), and the other in a 3'-OH group (the 3'-end). Nucleotide sequences are conventionally written in the 5' ^ 3' direction, which is also the direction of synthesis for all nucleic acids. Genetic information is encoded within the DNA molecule precisely as a sequence of nucleotides.

Thus, the backbone of a polynucleotide chain consists of alternating phosphate residues (each carrying a negative charge under physiological conditions) and pentoses, forming the sugar-phosphate backbone. Nitrogenous bases project from this backbone as side chains.

Fig. 1.3. Polynucleotide chain