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Part Ii - Molecular Biology

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Part Ii - Molecular Biology PART II - MOLECULAR BIOLOGY Module VII Nature of Genetic Materials Modern concept of gene (Cistron, muton, recon, viral genes). Brief account of the following-- Split genes (introns and exons), Junk genes, Pseudogenes, Overlapping genes, Transposons The term gene was introduced by Johanssen in 1909. Prior to him Mendel had used the word factor for a specific, distinct, particulate unit of inheritance that takes part in expression of a trait. Johanssen has defined gene as an elementary unit of inheritance which can be assigned to a particular trait. Morgan’s work suggested gene to be the shortest segment of chromosome which can be separated through crossing over, can undergo mutation and influence expression of one or more traits. Presently, a gene is defined as a unit of inheritance composed of a segment of DNA or chromosome situated at a specific locus (gene locus) which carries coded information associated with a specific function and can undergo crossing over as well as mutation. A gene is: A unit of genetic material which is able to replicate, It is a unit of recombination, i.e., capable of undergoing crossing over, A unit of genetic material which can undergo mutation, A unit of heredity connected with somatic structure or function that leads to a phenotypic expression. Modern concept of gene (Cistron, muton, recon, viral genes). After the discovery of DNA, the gene has been defined as cistron, recon and muton. The classical gene is the smallest unit that could undergo a mutational change. A gene further divided into smaller units of function, mutation and recombination. Symour Benzer (1955-USA) coined the terms cistron, recon, and muton to explain the relationship between DNA and genetic phenomena. (a) Cistron : It is the unit of function. Cistron represents a segment of the DNA molecule and consists of a linear sequence of nucleotides, which controls some cellular function. In E. Coli cistron may contain about 1500 base pairs. Some cistrons may contain as many as 30,000 base pairs. The cistron begin with initiation codon and ends with a terminating codon. Each cistron is responsible for coding one m-RNA molecule which in turn controls the formation of one polypeptide chain. Each cistron consists of hundreds of mutons and recons. (b) Recon : It is a unit of recombination. It is the smallest unit capable of recombining genetically. Recombination studies on microbes indicate that structurally the recon consists of one or two pairs of nucleotides, possibly only one pair. (c) Muton : It is a unit of mutation. The shortest chromosomal unit capable of undergoing mutation has been called the muton. The muton consists of one or many pairs of nucleotides within the DNA molecule. Types of Genes: 1. House Keeping Genes (Constitutive Genes): They are those genes which are constantly expressing themselves in a cell because their products are required for the normal cellular activities, e.g., genes for glycolysis, ATP-ase. 2. Non-constitutive Genes (Luxury Genes): The genes are not always expressing themselves in a cell. They are switched on or off according to the requirement of cellular activities, e.g., gene for nitrate reductase in plants, lactose system in Escherichia coli. Non- constitutive genes are of further two types, inducible and repressible. 3. Inducible Genes: The genes are switched on in response to the presence of a chemical substance or inducer which is required for the functioning of the product of gene activity, e.g., nitrate for nitrate reductase. 4. Repressible Genes: They are those genes which continue to express themselves till a chemical (often an end product) inhibits or represses their activity. Inhibition by an end product is known as feedback repression. 5. Multigenes (Multiple Gene Family): It is a group of similar or nearly similar genes for meeting requirement of time and tissue specific products, e.g., globin gene family (e, 5, (3, у on chromosome 11, oc and 8 on chromosome 16). 6. Repeated Genes: The genes occur in multiple copies because their products are required in larger quantity, e.g., histone genes, tRNA genes, rRNA genes, actin genes. 7. Single Copy Genes: The genes are present in single copies (occasionally 2—3 times), e.g., protein coding genes. They form 60—70% of the functional genes. Duplications, mutations and exon reshuffling can form new genes. 8. Pseudogenes: They are genes which have homology to functional genes but are unable to produce functional products due to intervening nonsense codons, insertions, deletions and inactivation of promoter regions, e.g., several of snRNA genes. 9. Processed Genes: They are eukaryotic genes which lack introns. Processed genes have been formed probably due to reverse transcription or retroviruses. Processed genes are generally non- functional as they lack promoters. 10. Split Genes: They were discovered in 1977 by many workers but credit is given to Sharp and Roberts (1977). Split genes are those genes which possess extra or nonessential regions interspersed with essential or coding parts. The nonessential parts are called introns, spacer DNA or intervening sequences (IVS). Essential or coding parts are called exons. Transcribed intronic regions are removed before RNA passes out into cytoplasm. Split genes are characteristic of eukaryotes. However, certain eukaryotic genes are completely exonic or non-split e.g., histone genes, interferon genes. Split genes have also been recorded in prokaryotes, thymidylate synthase gene and ribonucleotide reductase gene in T4. A gene that produces calcitonin in thyroid forms a neuropeptide in hypothalamus by removing an exon. Adenovirus has also a mechanism to produce 15—20 different proteins from a single transcriptional unit by differential splicing. 11. Transposons (Jumping Genes; Hedges and Jacob, 1974): They are segments of DNA that can jump or move from one place in the genome to another. Transposons were first discovered by Me Clintock (1951) in case of Maize when she found that a segment of DNA moved into gene coding for pigmented kernels and produced light coloured kernels. Transposons possess repetitive DNA, either similar or inverted, at their ends, some 5, 7 or 9-nucleotide long. Enzyme transposase separates the segment from its original by cleaving the repetitive sequences at its ends. There are many types of transposons. In human beings the most common types of transposons belong to Alu family (having a site for cutting by restriction enzyme Alu I). The number of nucleotides per transposon is about 300 with about 300,000 copies in the genome. Passage of transposons from one place to another brings about reshuffling of nucleotide sequences in genes. Reshuffling in introns often changes expression of genes, e.g., proto- oncogenes → oncogenes. New genes may develop by exon shuffling. Other changes caused by transposons are mutations, through insertions, deletions and translocations. 12. Overlapping Genes: Overlapping genes are defined as a pair of adjacent genes whose coding regions are partially overlapping. In other words, a single stretch of DNA codes for portions of two separate proteins. For two genes to overlap, the signal to begin transcription for one must reside inside the second gene, whose transcriptional start site is further “upstream.” Some of the benefits of overlapping genes are that they enable the production of more proteins from a given region of DNA than is possible if the genes were arranged sequentially. In the bacteriophage PhiX174, overlapping of genes is necessary. The amount of DNA present in the circular, single-stranded DNA genome of this virus is not sufficient to encode the eleven bacteriophage proteins if transcription occurs in a linear fashion, one gene after another. 13. Structural Genes: Structural genes are those genes which have encoded information for the synthesis of chemical substances required for cellular machinery. The chemical substances may be: (a) Polypeptides for the formation of structural proteins (e.g., colloidal complex of protoplasm, cell membranes, elastin of ligaments, collagen of tendons or cartilage, actin of muscles, tubulin of microtubules, etc.). (b) Polypeptides for the synthesis of enzymes, (c) Transport proteins like haemoglobin of erythrocytes, lipid transporting proteins, carrier proteins of cell membranes, etc. (d) Proteinaceous hormones, e.g., insulin, growth hormone, parathyroid hormone, (e) Antibodies, antigens, certain toxins, blood coagulation factors, etc. (f) Non-translated RNAs like tRNAs, rRNA. Broadly speaking, structural genes either produce mRNAs for synthesis of polypeptides/proteins/enzymes or noncoding RNAs. 14. Regulatory Genes (Regulatory Sequences): Regulatory genes do not transcribe RNAs for controlling structure and functioning of the cells. Instead, they control the functions of structural genes. The important regulatory genes are promoters, terminators, operators and repressor producing or regulator genes. Repressor does not take part in cellular activity. Instead, it regulates the activity of other genes. Therefore, repressor producing gene is of intermediate nature. 15. Tissue Specific Genes: They are genes which are expressed only in certain specific tissues and not in others. 16. Junk Genes A DNA sequence that is part of a genome and is not known to code for proteins or to regulate the expression ofgenes. Junk DNA may constitute up to 95 percent of the human gen ome and is postulated to be involved in theevolution of new genes and possibly the repair of genes. Gene Functions: (i) Genes are components of genetic material and are thus units of inheritance, (ii) They control the morphology or phenotype of individuals, (iii) Replication of genes is essential for cell division, (iv) Genes carry the hereditary information from one generation to the next, (v) They control the structure and metabolism of the body, (vi) Reshuffling of genes at the time of sexual reproduction produces variations, (vii) Different linkages are produced due to crossing over, (viii) Genes undergo mutations and change their expression, (ix) New genes and consequently new traits develop due to reshuffling of exons and introns.
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