Polymeric DNA is composed of four different nucleotides. Each nucleotide consists of a 2'-deoxyribose sugar, purine or pyrimidine base, and phosphate moiety. Purine bases are either adenine or guanine, whereas pyrimidine bases are either thymine or cytosine. When a base is linked to the 1' carbon of the deoxyribose sugar, it is referred to as a nucleoside.
Molecular Nutrition and Genomics: Nutrition and the Ascent of Humankind, Edited by Mark Lucock Copyright © 2007 John Wiley & Sons, Inc.
When, in addition, phosphate moieties are attached to the sugar, the structure is referred to as a nucleotide.
Nucleotide triphosphates (Figure 1.1) of adenine (A), guanine (G), cytosine (C), and thymine (T) are polymerized to form DNA via phosphodiester bond formation between the 5' phosphate of one nucleotide and the 3' hydroxyl group of the next nucleotide. The sequence of bases is what encodes the genetic blueprint for life. It can be read in the 5' ^ 3' or the 3' ^ 5' direction.
The primary sequence of DNA permits a three-dimensional structure to form, which is represented by a double helix. The sugar-phosphate linkage forms the molecular backbone
Uracil and its corresponding nucleotide:
hl th oh oh
Figure 1.2. RNA is the same as DNA except RNA contains uracil, whereas DNA contains thymine. Additionally, in RNA, ribose replaces DNA's 2-deoxyribose.
of this structure. The bases face inward and stabilize the double helix via hydrogen bonds between adjacent T and A bases, and again between adjacent G and C bases. This base pairing is specific, and purine always interacts with pyrimidine, a phenomenon referred to as "complementary base pairing." The double helix is right-handed with a turn every 10 bases. Examination of the structure reveals a major molecular groove, which facilitates protein interactions.
Complimentary base pairing ensures that the sequence of one DNA strand predicts the base sequence of the other. This simple fact is what permits the fidelity of the genetic blueprint to be preserved during replication of DNA as part of cell division, and during the expression of genes.
Expression of DNA, which is the conversion of the base sequence blueprint into an amino acid sequence within a functional protein, requires as a first step, the transcription of the DNA sequence into an RNA transcript. RNA is the same as DNA except RNA contains uracil, whereas DNA contains thymine (Figure 1.2). Additionally, in RNA, ribose replaces DNA's 2-deoxyribose. The RNA transcript is referred to as messenger RNA (mRNA). mRNA is then translated into a protein on the ribosome—transfer RNAs (tRNA) are small molecules that coordinate individual amino acids to form proteins that have been specified by the mRNA sequence.
This phenomenon of gene expression in which the biological data encoded by a gene is made available in terms of a functional protein is referred to as "the central dogma." That is, information is passed from DNA to RNA to protein.
Humans contain around 23,000 genes on 23 chromosomes. These genes are separated by intergenic (noncoding) DNA. Although a gene is the fundamental unit of information in that a single gene codes for a single polypeptide, higher organisms such as man also have multigene families. In their simplest form, a gene family contains more than one copy of a gene where its expression product is required in large amounts. Complex multigene families also exist. These yield similar, but distinct, proteins with related function, for example, the globin polypeptides.
To orchestrate gene regulation according to cellular need, gene promoter regions exist upstream from the coding region of a gene. Promoter sites bind the enzyme for synthesizing the RNA transcript (RNA polymerase II) and any associated transcription factors that are required to initiate mRNA synthesis. Promoter regions usually contain a TATA box around 25 base pairs upstream from the site at which transcription commences. Transcription factors bind DNA around the TATA box and orchestrate the binding of RNA polymerase II. RNA polymerases I and III are associated with transcription of ribosomal RNAs and genes encoding tRNAs, respectively.
Transcription factors can be considered as modular molecules that contain DNA binding, dimerization, and transactivation modalities. These regulatory factors exhibit characteristic structural motifs. The DNA binding modality contains three potential motifs: zinc fingers, basic domains, and helix-turn-helix motifs. Dimerization modalities contain two motifs: leucine zippers and helix-loop-helix structural motifs. The formation of homo-and heterodimers leads to transcription factor variation and, hence, a diversity of function. Transcription factors can act to both initiate and repress transcription.
Genes do not contain a continuous code; rather they are split into coding regions known as exons and noncoding regions known as introns. Introns are removed from the RNA transcript by a process referred to as splicing. This process occurs before protein synthesis.
Some genes have accumulated nonsense errors in their base sequence and no longer function. These archaic genes are referred to as pseudogenes.
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