Class 12 Molecular basis of Inheritance-II NEET AIIMS

Molecular basis of Inheritance-II

The structure of DNA consists of a linear sequence of deoxyribonucleotides.  This sequence ultimately dictates the components containing proteins, the end product of most genes.  In this foregoing discussion, the focus will be made on the initial phases of gene expression by addressing major questions.  First, how is genetic information encoded?  Second, how does the genetic transfer from DNA to RNA occur?  Third, how translation occurs, and finally, how gene regulates?

Gene Expression

l      Gene expression refers to the molecular mechanism by which a gene shows its potential in the phenotype of an organism.

Mechanism of Gene Expression

l      A gene contains the blueprint or code for a particular polypeptide in the form of a specific sequence of its pairs.  It transfers its code to mRNA transcribed from it.  The process is called transcription.  The mRNA binds to ribosomes and with the help of suitable tRNAs selects the required amino acids and links them in a proper sequence received from the gene to form a polypeptide.  This process occurs on the ribosomes and is called translation.

l      The polypeptide may contribute to a morphological or functional trait (phenotype) of the cell and organism.  Thus, the molecular structure of a gene is expressed in a phenotype.  There is a definite relationship between the genes and proteins present in a cell or an organism.  A change in the gene would change the code and give rise to a different polypeptide, ultimately a different phenotype.

Gene Expression in Eukaryotes

l      The genome of higher eukaryotes is very complex.  This is evident from the number of genes present in the eukaryotic cell.  Human haploid genome seems to have 30,000 to 40,000 genes.

l      The structure of the eukaryotic gene is also complex.  Whereas the concept of colinearity of gene and protein is fully true for the prokaryotes, it partly holds good for the eukaryotes.  This is so because a eukaryotic gene has stretches of the base, which do not code for amino acids inserted between stretches of the base, which are code for amino acids.  The coding segments of the gene are called exons and noncoding sequences are called introns

l      The mRNA transcribed from a eukaryotic gene is called hnRNA and these non-coding sequences are removed by the process of post-transcriptional processing which is known as splicingThus, the processed mRNA and polypeptide it codes for are colinear even in the eukaryotes, although the genes are split.  The processed mRNA passes out of the nucleus and joins the ribosomes.  Here it is expressed through the synthesis of a polypeptide.

l      Each reaction is enzyme controlled and enzymes are gene controlled, i.e., gene (B) ultimately is responsible for the reaction,  because it is responsible for the production of enzyme b.  If we get mutants of the gene (B), which failed to produce the enzyme b, then the reaction would not take place and if B were indispensable to the cell, growth would cease.

l      It is known that changes in gene mutations occur spontaneously with a low frequency.  The probability that a given gene will mutate to a defective form can be increased a hundredfold or more by mutagenic agents.

l      Neurospora crassa (Red mould), a fungus of class Ascomycetes, is composed of intertwined hyphae.  Each cell contains a haploid nucleus.  It reproduces asexually by conidia and sexually by contact between an antheridium of + strain with the ascogonium (reproductive structure) of – strain.

l             Later a fruiting body called perithecium is developed as a result of sexual reproduction.  The perithecium develops many asci (singular-ascus).  In each ascus, the mother cell nuclei of opposite type fuse (diploid phase is of short duration) but soon meiosis takes place as a result of which 4 haploid ascospores are formed (two of + strain and two of –strain).  Each mesopore then divides mitotically, thus forming eight ascospores (four of + types and four of – type).  The ascospores germinate to give rise to the new mycelium.  Neurospora completes its life cycle in only 10 days.

l      Neurospora can be grown in pure culture on a chemically known medium containing only nitrate, sulphate, phosphate, various other inorganic substances, sugar and biotin, a vitamin of the B group. From these simple elements, the mould produces all the constituent parts of its protoplasm.  These include 20 amino acids, 9 water-soluble vitamins from the B group and many other organic molecules of vital significance.

l      The red mould experiment to test the hypothesis that genes control enzymes and metabolism is carried out as follows :

·               Ascospores are X-rayed or otherwise treated with mutagenic agents.  Mutants are produced that will not grow unless some specific compound (Like B) is supplied.

Figure: The production and isolation of mutations in Neurospora affecting single chemical reactions. The sequence of steps illustrated demonstrates that a mutation has been induced which affects the synthesis of vitamin, thiamine.

·       That enzymes are synthesized under gene control as given above have been established by the work of Beadle and Tatum (1944).  They formulated one gene-one enzyme hypothesis which states that “a gene exerts its influence on the phenotype through its role in the production of an enzyme”.  For this work, Beadle and Tatum were awarded Nobel Prize in 1958.

·       However, now we know that one gene induces the synthesis of one polypeptide. A single polypeptide may itself be an enzyme.  But in many cases, properly functional enzyme arises only after several polypeptides of the same or different kinds have been combined.  Therefore we should substitute the formulation of one gene-one polypeptide for the statement of one gene-one enzyme; each gene engages in character formation via the induction of a gene-specific polypeptide/enzyme.

The Central Dogma of Protein Synthesis

l             The path for the flow of genetic information has been termed by Crick (1958) as central dogma. It proposes a unidirectional or one-way flow of information from DNA to RNA (transcription) and from RNA to a polypeptide (translation).

l Temin (1964) reported the reverse flow of genetic information i.e., from  RNA to DNA in retroviruses (reverse transcription).  However, Commoner (1968) suggested a circular flow of information.

l             This reverse transcription was brought about by an RNA dependent DNA polymerase called reverse transcriptase, which was reported separately by T.H. Temin and D. Baltimore in 1970 (Central dogma reverse in retroviruses).  Temin was awarded  Nobel Prize for this in 1975.

l      Transcription occurs over DNA and translation occurs over ribosomes.  The two are separated in time and space.  If both were in the nucleus, the ribosomes would be exposed to respiratory breakdown.  The nuclear envelope preserves the stability of the DNA by protecting it from respiratory enzymes and RNAs from nucleases.