Biochemistry and Molecular Biology - Belyasova N.A. 2002

Molecular Foundations and Mechanisms of Heredity
Organization of the Cellular Genetic Apparatus
Gene Structure and Function. Organization of Genes in Chromosomes

The term "Gene" was introduced by the Danish scientist W. Johannsen in 1909, at a time when its material nature was still unknown. The understanding of gene Structure and function was greatly advanced by the experiments of American researchers G. Beadle and E. Tatum, who studied the biochemical role of various genes in the fungus Neurospora crassa. They established a clear one-to-one correspondence between the appearance of an X-ray-induced genetic mutation and the loss of a specific enzyme required for a given metabolic step. Based on this, Beadle and Tatum formulated the "one gene — one enzyme" hypothesis, which posited that each gene directs the synthesis of a single enzyme. Today, this hypothesis has undergone only one major refinement: the realization that The structure of certain Proteins comprising more than one polypeptide chain is encoded by multiple genes. In these cases, the Amino Acid Sequence of each polypeptide chain is encoded by a separate gene, synthesized independently, and only subsequently assembled into the final product. Most often, the genes controlling the synthesis of two or more polypeptide chains are located close to each other on the chromosome, though not always. For example, the genes determining the STRUCTURE OF THE $\alpha$- and $\beta$-chains of Hemoglobin are unlinked. Thus, the modern interpretation of the Beadle-Tatum postulate is "one gene — one polypeptide chain." This discovery laid the groundwork for deciphering the Mechanisms of Genetic information expression.

Today, a gene is understood as the structural unit of hereditary information that is functionally indivisible. A gene is a segment of a DNA molecule (or, more rarely and exclusively in certain Viruses, an RNA molecule) that encodes the structure of a single macromolecule: a polypeptide, tRNA, or rRNA. While the Structure of Prokaryotic, eukaryotic, and viral genes—as well as their chromosomal Organization—share many common features, There are also significant differences.

The prokaryotic nucleoid contains approximately 2–3 thousand non-overlapping genes, which are categorized into independent genes and grouped genes. Independent genes are so named because the mRNA transcribed from such a gene is always monocistronic (a Cistron being defined as a nucleotide sequence encoding a single polypeptide chain or stable RNA). In turn, independent genes in prokaryotes may contain regulatory regions (Fig. 1.6, A)—in which case their METABOLISM/31.html">Transcription is subject to regulation—or they may lack them. The latter are termed constitutive genes because their transcription occurs continuously (constitutively), regardless of the cellular state. Constitutive genes encode constitutive proteins.

In most cases, however, Prokaryotic Transcription units are polycistronic, containing sequences that encode not just one, but several types of proteins or RNA (Fig. 1.6, B and C). As a rule, the transcription of coding sequences within a polycistronic unit is coordinated, involving shared 5'- and 3'-regulatory elements. The sequences encoding one or more Polypeptides are transcribed into a mature mRNA that undergoes no modification events prior to Translation. Conversely, sequences encoding Different types of RNA are specifically cleaved during post-transcriptional Processing to yield mature, stable RNA products.

Thus, the Modern concept of the prokaryotic gene encompasses the following elements: 1) transcription units that include sequences encoding mature RNA or a polypeptide, 5'-leader and 3'-trailer sequences, as well as spacer DNA; 2) 5'-sequences required for the accurate initiation of transcription (the promoter) and 3'-sequences necessary for its proper termination (the terminator); and 3) sequences that regulate the frequency of Transcription initiation.

Figure 1.6 illustrates all these elements found across various prokaryotic genes. A transcription unit represents the DNA segment between the sites where transcription begins and ends. Protein-coding genes are characterized by the presence of a specific number of NUCLEOTIDES within the transcription unit that either precede the protein-coding sequence (the 5'-leader) or follow it (the 3'-trailer). These elements are present in mature mRNAs, and the 5'-leader sequence is known to play a role in regulating transcription.

Spacer DNA consists of intervening sequences that separate coding regions and are removed during the processing of primary transcripts. The sequences required for the correct initiation of transcription primarily include the promoter—to which RNA polymerase binds—and regions that influence The rate of initiation (the operator and activator). Nucleotide sequences responsible for transcription termination are located at the 3'-end of the gene.

In the nucleoid, genes follow one another almost continuously along the entire length of the DNA, and occasionally (in very rare cases) even overlap. A significant portion of prokaryotic genes are functionally organized into groups. For instance, the genes for Amino acid Biosynthesis and Carbohydrate Catabolism pathways in prokaryotes are frequently organized into operons, allowing their expression to be coordinately regulated.

The number of genes in Eukaryotic Genomes is typically an order of magnitude greater than in prokaryotes. For example, The Human Genome is estimated to contain 40–60$\times$10³ genes. The organization within eukaryotic Chromosomes and the structure of the genes themselves exhibit several distinct features. First, unlike Prokaryotic Cells where transcription relies on a single type of RNA polymerase, Eukaryotic Transcription involves multiple distinct Enzymes. Consequently, the transcription units themselves and their regulatory sequences feature greater complexity and structural diversity. Second, eukaryotic genomes abound in mosaic transcription units in which coding sequences (exons) alternate with non-coding sequences (introns). Introns are most frequently found in genes encoding polypeptides and tRNAs, and less commonly in rRNA genes. The size, number, and Location of introns vary among different genes. Overall, the total length of intron sequences exceeds the combined length of exons by a factor of 2 to 10 or more. Introns are excised from mRNA during splicing. A third characteristic of eukaryotic genes is that all protein-coding mRNAs are monocistronic and are not grouped into operons. Genes for 5S rRNA are arranged in tandem repeats within eukaryotic chromosomes (appearing as multiple sequential copies), but each gene is transcribed from its own promoter to produce an RNA molecule containing only a single 5S rRNA sequence per molecule. In contrast, Other types of rRNA form clusters (closely spaced groups of genes with a shared promoter) and are transcribed as a polycistronic RNA molecule, which undergoes post-transcriptional processing to yield mature 18S, 5.8S, and 28S rRNA molecules. The gene count in various eukaryotic genomes varies widely, approaching 10⁵.

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Fig. 1.6. Structural Features of prokaryotic genes

Viral genomes have the smallest number of genes, typically up to ten. A key feature is their ability to overlap genes by utilizing multiple reading frames of The Genetic Code. This method of storing hereditary information increases the coding capacity of the genetic material, which is essential for viruses given the limited size of their capsids, which can only accommodate a strictly defined amount of nucleic acid.