One Gene-One Polypeptide Concept

In this article we will discuss about the One Gene-One Polypeptide Concept.

It is a fact that hereditary characters are maintained and transmitted from one generation to another through DNA molecules, because DNA can duplicate itself and duplicated molecules can be passed on to the offsprings. The general activity of genes brings about expression of hereditary traits in the organism.

Now the main questions are as to how the genes (DNA molecules) govern the biosynthetic processes of the cells and how these genes control the phenotypic properties of the organisms. The answers to these basic questions were sought in the relationship between genes and specific biochemical reactions.

The heritable changes that geneticists first studied were necessarily those which could most easily be observed. An English physician, Sir Archibald Garrod, made penetrating study of some rare hereditary diseases in human and recognised that certain biochemical deficiencies were caused by enzymatic abnormalities. On the basis of his studies on congenital (existing from the birth) diseases of human.

Sir Garrod safely suggested relationship between genes and enzymes. The idea that the action of a gene is concerned with the formation of particular enzyme was ignored by most geneticists for some thirty years.

James B. Summer of Cornel University and John H. North Rop of Rockefeller Institute between 1926 and 1930 showed that enzymes are proteins. The idea about gene and enzyme relationship was revived by George W. Beadle and Edward L. Tatum (1941).

From the studies on heritable metabolic abnormalities of the fungus, Neurospora crassa, they concluded that all the intermediary biosynthetic steps of a metabolic process were governed by distinct genes. Beadle and Tatum formulated the one gene -one enzyme concept in 1944. The theory states that a gene exerts its influence on the phenotype through its role in the production of an enzyme.

Beadle and Tatum studied the genie action in neurospora crassa. Normally the fungus can grow on minimal culture medium containing agar, sucrose, nitrate, inorganic minerals and the only vitamin biotin. This means that this organism can synthesize all other vitamins and amino-acids which are required in its metabolism.

When the conidia of this fungus are treated with mutagenic agents (say. X-ray), some of them become unable to grow on minimal medium.

These mutant spores are then tested systematically by adding particular vitamins, amino-acids, etc. to the minimal medium to determine what substance or substances they are unable to synthesize. The mutants can be crossed with normal or wild type and their products of meiosis, the 8 ascospores, may be individually tested for their nutritional requirements.

If an arginine requiring strain (a -) is crossed with normal strain (a +), all the 8 ascospores can grow in a medium containing arginine, but only 4 ascospores can grow in a medium lacking arginine. This indicates that a single gene has mutated.

The arginine requiring mutant may be more complex because, as shown in the following chain, arginine synthesis involves a chain of intermediate steps; each reaction is controlled by one gene. Three steps have been noted in the conversion of glutamic acid to arginine and each of them has been found to be controlled by one gene.

The mutation of a single gene leads to the suppression of one step. This can be demonstrated by growing mutant on minimal medium with that substance which cannot be synthesized. In several biochemical studies, the extracts of neurospora have shown that tryptophan like arginine is synthesized in a sequence of chemical reactions.

Mutations in tryptophan require strains map at several genetic locations. Each mutant is defective in one of the steps in biosynthetic sequence. The mutation in a specific chromosomal region is reflected by the loss of activity of one enzyme. Thus basic gene enzyme relationship is clear.

Recent researches have verified the basic conclusion about gene-enzyme relationship. Currently the Beadle and Tatum’s concept of one gene-one enzyme has been revised to one gene-one polypeptide chain (protein) in view of the complexity in the structures and the functions of enzymes. The modem researches have proved that gene is DNA which is directly concerned with the synthesis of particular protein.

Gene Action:

The expression of genes by genetic transcription into complimentary RNA sequences and subsequent translation of hereditary information contained in mRNA into polypeptide chain which forms the ultimate product of gene action is called primary gene action.

The analysis beyond primary action of gene is greatly complicated by the integrated state of cellular and developmental metabolism, by the remoteness of the phenotype from the primary gene action and the number of intervening steps influenced by other genes (gene interaction) and by environmental factors (gene activation).

In prokaryotes the transcription and translation of genetic information occurs in one cell compartment whereas in eukaryotes the two processes are accomplished into two separate compartments of a cell, i.e., nucleus and cytoplasm. In addition, some genetic information (organelle DNA) is also present and utilized within certain cytoplasmic organelles particularly plastids and mitochondria.

The operation of nuclear and extra-nuclear genomes is coordinated by some mechanism which is not yet fully understood. The genetic regulation of primary gene action in strict sense of the term occurs only at the level of transcription.

The whole series of biochemical processes which lead from a gene to the phenotypic expression by which it is recognised is referred to as gene action system (Waddington, 1962).

Thus gene has two essential functions:

(i) Replication or self-reproduction; and

(ii) Intervention in mechanism by which the phenotype of organism is produced in a given environment (phenogenesis).

Primary Gene Action (Gene and Protein Synthesis):

The genotype (total genetic material) of the cell determines the potential type of proteins and also determines their relative amounts in the cell. Proteins serve as structural components of the cells which make up the framework of living body. Special types of proteins which act as catalysts in bringing about numerous chemical reactions and control them precisely are called enzymes.

In fact, all functions of the living system are carried out by proteins. Thus from the structural as well as functional point of view proteins are important constituents of the cells, or in other words, proteins constitute the fundamental molecular machinery of the cell.

Genes act by controlling the structure and the rate of production of specific proteins (enzymes). Genes are segments of DNA molecule. The DNA of each gene forms a complimentary mRNA strand which attaches to the ribosomes where it serves for coding of a protein (enzyme).

The sequence of aminoacids in protein (i.e., the structure of protein or enzyme) is determined by the sequence of nucleotides in mRNA which in turn is determined by the sequence of nucleotides of DNA (gene).

A series of enzyme controlled reactions determine traits in an organism. Since the structure of these enzymes is controlled by genes it follows that genes determine traits.

The whole events may be summarized as follows:

The basic building blocks of proteins are amino acids. Excepting proline, all other amino acids have a common structure consisting of a central carbon atom (the a-carbon) to which is linked a-amino group (- NH₂), an α-carboxyl (- COOH) and a hydrogen atom (proton). The other part of aminoacid is called the R-group which varies from one aminoacid to another. It is R-group that gives the aminoacid its chemical properties.

The general formula of an aminoacid is illustrated below:

Proteins are polymeric molecules and are formed by combination of many amino acid molecules in linear sequence. The amino acids are joined with one another through special type of bond, called peptide linkage.

This peptide bond is established by elimination of a molecule of water between carboxyl (- COOH) and amino (- NH₂) groups of adjacent amino acids. The peptide bond is of amide (- CONH -) type.

An example of peptide bond formation is given below:

In this way, many amino acids are joined end to end by peptide bonds making a long chain. One end of protein chain contains amino (NH₂) group (amino end) and the other contains carboxylic (- COOH) group (carboxylic end).

The linear chain of amino acids formed in this manner is termed as polypeptide chain or protein. The formation of polypeptide linkage requires the action of enzyme peptide polymerase and energy rich compound guanosin triphosphate (GTP).

In living system about 20 out of 22 different amino-acids are known to take part in the protein synthesis. These are mentioned in the Table 20.1.

The molecular weight of protein depends upon the length of molecule and number of amino acids in it.

Proteins are recognised by four structural levels:

(i) Primary structure:

It is the linear sequence of aminoacids in a polypeptide chain. The newly synthesized polypeptide chain is called primary protein.

(ii) Secondary structure:

When the primary polypeptide chains are twisted or coiled into a helix, electrostatic bonds are formed between – COOH group and NH₂ group and hydrogen bonds develop between amino acids facing each other due to coiling. Such proteins are said to be secondary proteins. In biological proteins, the polypeptide chains remain coiled either in a like shape or in p like shape and hence they are called a helix and P helix respectively.

(iii) Tertiary structure:

When very long polypeptide chain becomes extensively folded and coiled in order to compress the long spiral chain into a globular form and subsequently certain intra chain bonds, specially disulphide (- S – S -) bridges between cysteine residues of polypeptide chain over a vast surface to create interstices between the polypeptide chains, a tertiary structure of protein is resulted.

The tertiary structure of a protein often places hydrophobic (water hating) groups on the outside and hydrophilic (water loving) groups on the inside. Examples are insulin enzyme, ribonuclease enzyme etc. The most tertiary proteins act like catalysts or enzymes.

(iv) Quaternary structure:

The association of more than one polypeptide chain to form stable unit corresponds to the quaternary structure. Quaternary proteins result when inter chain bonds or bridges are established so as to link two or more otherwise independent polypeptide chains. Most proteins with molecular weight higher than 20,000 possess quaternary structure and are composed of more than one polypeptide chain.

The best example of quaternary protein is haemoglobin (molecular weight 1, 00,000) which is formed of two a-and two P-chains. The chemical and biological individuality of a protein depend upon the order in which amino acids are linked in it. So in a particular protein chain aminoacids are arranged in correct order.

But can these aminoacids be so precisely arranged? Yes, it is so, and this precision in the sequence of aminoacids during the synthesis of protein is controlled by DNA molecule which itself is not directly involved in the synthesis. Actually DNA molecules send their message to the sites of protein synthesis through special type of RNA called messenger RNA or mRNA.

The information for the structure of polypeptide (protein) is stored in a polynucleotide chain. The sequence of bases in a polynucleotide chain determines the sequence of amino acids in a particular polypeptide.

The transfer of information from DNA to wRNA and then from wRNA to protein (aminoacid sequence) is unidirectional according to Francis Crick (1956) and it does not flow in reverse direction i.e., from protein to RNA to DNA.

The DNA molecule is provided with the information for its own replication. Francis Crick termed this flow of information from DNA to RNA to protein molecule as central dogma. This is shown in Fig. 20.1.

The central dogma of molecular biology, therefore, involves the following three major processes for preservation and transmission of genetic information:

1. Replication:

A process which is indicated by the arrow encircling DNA signifying that DNA is template for self-replication.

2. Transcription:

The arrow between DNA and RNA indicates that all cellular RNAs are synthesized on DNA templates.

3. Translation:

This is process by which all proteins are determined by RNA templates on the ribosomes.

In certain cells infected with RNA viruses, e.g., TMV, φMS₂, φR₁₇ etc., the viral RNA produces new copies of itself with the help of RNA replicase. Genetic RNA of some viruses, e.g., RSV, sometimes acts as a template for the production of complementary strand of DNA (reverse transcription).

On this ground Barry Commoner (1968), however, suggested that flow of information should be cyclic rather than in one way, but such reversals of normal flow of information are rare events.