The Concept of Gene

Genes are regarded as the biological units, which design development, control metabolism, govern heredity, generate mutations and produce heritable variations.

They are the molecules which govern the morphological, anatomical, physiological, behavioural, reproductive and developmental aspects of organisms.

In 1903, Sutton and Bouveri put forweard the "chromosome theory of heredity" and established that heredi tary factors are located in chromosomes and so chromosomes are the physical basis of heredity. In 1909, Johannsen coined the term "gene" to designate the hereditary determiner.

Classical concepts of gene:The concepts about genes, formulated before the birth of molecular genetics, are often

described as classical concepts. Their major generalizations are the following:

(i) Genes are independent, self-duplicating, hereditary units which determine the physical ,physiological and behavioral aspects of organisms.

(ii) Genes are the ultimate units of function that  express themselves through the production of proteins.

(iii) Genes are the fundamental units of recombination, mutation and variation.

(iv) Genes are the units of hereditary transmission, and they can be transmitted from one

generation to the next, without considerable changes in them.

(v)Genes have linear and non-overlapping arrangement in the specific points or loci of chromosomes.

(vi )A single chromosome contains hundreds of thousands of genes. A single gene may exist in alternative  forms, known as alleles, which occur in pairs. Most genes have only two alleles, dominant and recessive. But, some may have multiple alleles

(viii)two or more genes often interact to produce a single effect (interaction of genes)

Modern concepts of gene

 (i) Genes are complex hereditary determiners, composed of nucleic acid which is  sequences of nucleotides, which contain the information necessary for all biological functions.

(ii) The nucleotide sequence of a gene encodes the amino acid sequence of a polypeptide or protein.

(iii) Genes are mostly sequential and non-overlapping.

(iv) Genes are not the units of either function or recombination or mutation, but these are all the functional aspects or properties of genes.

(v) In some cases (e.g, bacteria), some closely associated genes behave as a single functional unit, known as operon. An operon governs the production of the enzymes of a metabolic pathway. It may include four kinds of genes, namely structural gene, operator gene, regulator gene and promoter gene. Structural gene codes for an enzyme.

Cistron:Cistron (Benzer -1957) is the fundamental genic unit, which governs the synthesis of a polypeptide chain or protein molecule (now-a-days the term cistron is used as a synonym of gene). A DNA molecule contains many cistrons. The mRNA of eukaryotes is monocistronic, while that of prokaryotes is polycistronic. A cistron, in turn, has several functional units, called codons. Each codon codes for a specific amino acid. It is formed of a set of three nucleotides and hence called triplet codon.

Muton:Muton (Benzer 1957) is the basic unit of gene mutation. In other words, it is the smallest unit of DNA, that can be altered in the formation of a mutation. Since mutation can occur even by a change in a single base, a single nucleotide pair can serve as a muton.

Recon:Recon (Benzer 1958) is the smallest genetic unit, capable of recombination . It may be formed of one or more nucleotide pairs. It is exchangeable but not divisible by genetic recombination. A cistron may contain several recons .

Complon :Complon is the unit of allelic complementation. It is almost similar to a cistron. Complementation is the process in which two mutant alleles together perform a function, which cannot be carried out by any one of them alone.

Transcripton:Transcripton is the unit of transcription, and it govems the synthesis of an RNA molecule. It is usually monocistronic in eukaryotes, and polycistronic in prokaryotes.

SPLIT GENES:Split genes (mosaic genes or interrupted genes) are the non-contiguous eukayotic genes with  informative or coding sequences, interspaced with or interrupted by long stretches of non-informative or non-coding "silent" or "spacer" sequences. Thus, split genes appear to be complex and fragmented genes, split up into alternating coding and non-coding regions. The non- coding regions are commonly called junk DNA or introns .The coding units are called exons, and the intervening non-coding regions are called introns or inserts, or intervening sequences (the terms exons and introns were coined by Walter Gilbert in 1978). Introns and split genes are very rare, or absent, in prokaryotic, mitochondrial and chloroplast DNAs, but relatively numerous in most eukaryotic nuclear genomes.They are present in some animal viruses also. Intron size varies from less than 100 to over 10,000 base pairs.

All exons may undergo transcription and translation. So, they find their expression in the pimary, intermediate and final products (i.e. in pre-mRNA, mature mRNA and proteins).On the other hand, introns are only transcribed to the pre-mRNA and then sliced out during the post-transcriptional chemical processing of immature mRNA. This is called mRNA splicing

Thus, introns appear only in the primary mRNA transcript and never in mature mRNA and proteins. On the whole, eukaryotic genes appear to be fragmented or interrupted, and they are expressed only after the splicing or excision of their introns during mRNA processing Split genes were discovered in 1977 by Richard. J. Roberts and Phillip Sharp (1993 Nobel Prize recipients), while studying the genetic material of adenoviruses (viruses which cause common cold, conjunctivitis, etc.). This discovery was a surprise jolt to the colinearity of genes and their products.

Features of split genes

Some of the features, common to all split genes, are the following:

(i) The organization of split genes would be consistently the same in all tissues of an organism.

(ii) Exons have precisely the same order in the split gene and also in its primary and secondary mRNA transcripts.

(iii) Introns, all by themselves, do not have any coding function. But, exon-intron combination codes for maturases. Maturases (Lazowska et al 1980, Cech 1985) are the proteins encoded by exon-intron combination. They catalyse the excision of introns from the primary transcript and the subsequent splicing of exons.

(iv) The presence of introns is neither essential nor deleterious to the organism.

(v) All split genes begin with an exon, and also end with an exon. The primary mRNA, transcribed from a split gene, is known as heterogeneous nuclear RNA (hnRNA) or precursor mRNA (pre-mRNA). t might be an exact replica of the split gene, with altemating exons and introns. Before its transformation to mature mRNA, it undergoes a chemical tailoring". Its introns are very carefully sliced away by excision enzymes (exo and endonucleases). Soon, the exons are spliced together by maturases (RNA ligases). If mutanon takes place in introns, maturases will not be produced, or modified maturases without splicing powers will be produced.

Significance of split genes

The significance of split genes is not definitely understood. Still, they are obviously advantageous to organisms in the following ways:

(I) Split genes provide an ingenious device for accommodating more DNA than what is actually required for the functioning of genes.

(ii) They enable the storage of the genetic information within minimum DNA.

(iii) The different exons of the same split gene can code for the different active sitesot a protein molecule (e.g., antibody genes).

(iv) Several proteins with the same amino acids can be formed from the same split gene that has many exons.

(v) Exons and introns allow flexibility in the synthesis of a variety of gene products.

PSEUDOGENES:Pseudogenes (Jacqet al-1977) are the mutant, imperfect and non-functional genes, which are strikingly homologous to their functional counterparts at different loci. In fact, they are the divergent members of gene families, which have become non-functional through mutations in the course of evölution. They have sequences coresponding to the exons and introns of functional genes. Still, they have no transcriptional and translational powers for want of promoters. Ihis is due to mutational changes. So, pseudogenes are only the defective and non-functional copies of functional genes, without powers for expression. They are produced by the mutation of active ancestral genes. The functional genes, which are homologous to the pseudogenes, are called productive genes. Pseudogene-producing mutations are mostly nonsense mutations, which generate stop codons and result in premature temination of translation. Some pseudogenes differ from their parent genes in having lost their introns. Curently, pseudogenes are regarded as a kind of "debris or evolutionary relics", accumulated in the genome as the "dead ends of evolutionary processes Pseudogenes area common feature of many eukaryotic gene families. The gene families of human actin genes, alpha and. beta globin genes, immunogobulin genes, etc. contain pseudogenes.

Features of pseudogenes

i) Most pseudogenes out number their normal counterparts. So, they are mostly repetitive sequences

(i) Most pseudogenes are flanked by short repetitive sequences. This possibly suggests their insertion to a target site.

CRYPTIC GENES :These are the inactive or phenotypically silent prokaryotic genes which have been silenced by a single nucleotide substitution. They remain unexpressed during the normal life cycle of the organism.

However, they may be reactivated by mutation, recombination,transposition and other genetic events or sometimes by changes in environmental conditions. Thus, the cryptic state of these genes is only a transient feature.

Oscillations between cryptic and active states do occur under the influence of genetic and environmental factors. Consequently, they are believed to confer some selective advantage on the organisms which carry them.