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.
(x) Genes change their expression due to position effect and transposons.
(xi) Differentiation or formation of different types of cells, tissues and organs in various parts
of the body is controlled by expression of certain genes and non-expression of others,
(xii) Development or production of different stages in the life history is controlled by genes