INTRODUCTION:The covering whole idea of gene since long

INTRODUCTION:The concept of gene is basic and fundamental part in all relevant fields of biological science (genetics, molecular etc.).There have been a lot of effort to define a concrete, covering whole idea of gene since long years ago. However, the concept still today being incomplete, updated time to time. Some authors consider that a gene includes the regulatory sequences required for its expression. Inclusion of regulatory sequences expands the term ‘gene’ from a specification of ‘what it is’ to indicate also ‘how it is used’. In order to provide a structure for understanding the concept, its history, transitional period and present status is divided into classical, neo-classical and modern periods described as follows:  DISCUSSIONS:·        Classical concept:      The word “gene” have been coined by Johannsen in 1909, Indeed, Johannsen thought of the gene as some form of calculating element , however,  much early theories of heredity proposed that offspring were concoction of fluids derived from one or both parents and that inherited characteristics were somehow determined by properties of these fluids. Biologist up to time of Charles Darwin, including Darwin himself, believed that inherited characteristics were literally dissolved like sugar in water (smcg.ccg.unam.mx/enp-unam/03-Estructura Del Genoma/geneDefination.pdf). However, definition of Johannes was based on concept of G. Mendel in 1866 worked by three scientist later on. Mendel do talk about some inheritance elements in his work which we today call gene but could only describe its abstract and not the complete properties. Further, American geneticist T.H. Morgan defines gene as linear arrangement and were able to cross-over and recombined in further generation (Morgan et.al. 1915). The classical theory of the gene defined the chromosomes as a linear array of genes, each occupying a fixed position on the chromosomes. The classical view prevailed into the 1930s, and conceived the genes as an indivisible unit of genetic transmission, recombination, mutation, and function. As A. Sturtevant and G. W. Beadle wrote in (1939), near the end of what we are calling the classical period of genetics, it was also clear that genes determine the nature of developmental reactions and thus, ultimately, the visible traits they generate. But how genes do these things was unknown (http://www.genetics.org/content/205/4/1353). Oliver (1940) discovered recombination in Drosophila melanogaster between two sex-linked allelic eye character mutants called Lozenge. In the case of Drosophila melanogaster, the biochemical nature of the characters of the genes that showed intragenic recombination was unknown. Detailed evidence of intragenic recombination within genes that supported one gene-one enzyme hypothesis was obtained from studies of micro-organisms, where selective technique for observing rare intragenic recombinants was easily observed .Beadle and Tatum stated gene as enzyme/polypeptide (1940s) and formulated “one gene” hypothesis. In addition to recombination, genetic complementation was of crucial importance in defining genes and gene functions in the classical theory of the gene. ·        Neo-classical concept:In this concept, the phenomenon of genetic complementation remained a criterion for the definition of gene. Certain definitive criteria distinguishing between intragenic and intergenic complementation made it possible to use the phenomenon of genetic complementation as crucial criterion in defining genes and gene function. The example of complementation was shown in Neurospora crassa, most extensively by Fincham (1966). The complementation relationship of whole series of mutant can be represented diagrammatically on a complementation map. This complementation map provides general interpretation and aspects of gene function. But before that, in late 1940s Avery and his colleagues showed that DNA is the hereditary material by demonstrating that the causative agent in bacterial transformation, which entailed a heritable change in the morphology of the bacterial cells (Griffith 1928), was DNA (Avery et al. 1944). Furthermore, in 1953 two scientist, James Watson and Francis crick, were trying to put together a model of DNA and discovered the double helix structure. This was a major breakthrough for the DNA theory of inheritance at that time. In this view, the gene (or cistron, as it was called then) was subdivided into constitutional parts, muton and recon, identified as nucleotides. In this concept conceptual framework of gene and gene function, one gene –one enzyme was replaced by one cistron –one polypeptide hypothesis.  Each cistron was believed to be responsible for synthesis of single mRNA and finally into polypeptide (https://www.ncbi.nlm.nih.gov/pubmed/12187434). Jacob and Monad (1961) in their stimulating article formulated “one gene – one messenger RNA” hypothesis according to which gene coding for protein was responsible for the synthesis of messenger RNA molecule that transmitted the genetic information present in the nuclear DNA to ribosomes located in the cytoplasm. Genes were units of transcription coding for messenger RNA.  Similarly the  co-linearity hypothesis assume that the linear structure of gene determines the linear primary structure of the corresponding polypeptide or more precisely, that the nucleotide sequence of the gene determines the amino acid sequence of the polypeptides. The gene occupies a space in locus which is sub divided into muton and recon, these unit being equivalent to one nucleotides pairs of DNA ,occupying a site of gene. This prevailed from 1955 to the 1970s (https://www.jstor.org/stable/2829967). With the advancement in cloning and sequencing technique, in late 1970s gene was defined as predicted sequence rather genetics locus responsible for a phenotype (Griffith and Stotz 2006). However, a gene effectively became identified as an annotated Open Reading Frame (ORF) in the genome.  An open reading frame is a span of genetic material that can be read by genetic machinery to produce a protein, one of the functional players in the cell. Genetic material — DNA and RNA — is written in a code that tells genetic machinery what to do. Researchers can scan the genome for open reading frames to find genes that encode for proteins (https://www.broadinstitute.org/blog/what-orf ).As the time passes, the definition of gene has progressed and reached to the new level of interest, which now leads to formation of modern theory. ·        Modern concept:Lots of efforts is being made to come up with concrete and physical idea of gene with full-prove evidence but however, there’s always been contrary and exception to such definitions. Both the classical and neo-classical concept the gene is no longer affixed point in the chromosome, defined by cis – trans test and producing a single messenger RNA. The major definition of genes up to now was somehow limited to prokaryotic organisms. That’s why the concept of Splicing and trans- splicing of genes come into existence. According to Berget et al.(1977), gene was not a simple unit of heredity or function, but rather a series of exons, coding for, in some cases, discrete protein domains, and separated by long noncoding stretches called introns. With alternative splicing, one genetic locus could code for multiple different mRNA transcripts.Recently, according to singer and Berg (1991) “A eukaryotic gene is combination of DNA segments that together constitute an express-able unit, expressing leading to the formation of one or more specific functional gene products that may be either RNA molecules or polypeptides”. In molecular terms, a gene is defined as entire nucleic acid sequence that is necessary for synthesis of functional polypeptides. According to this definition, a gene include more than nucleotides encoding amino acid sequence of proteins, referred as coding region (http://www.ncbi.nlm.nih.gov/books/NBK21640). The above definition is widely preferred by many biologist. Consequently, we all come to the point that the concept of gene to be simple, general, open and most abstract and depends on the context in which the terms is used.  However, modern discoveries include those of repeated genes, split genes and alternative splicing, assembled genes, overlapping genes, junk DNA, transposable genes, complex promoters, multiple poly-adenylation sites, poly protein genes, editing of the primary transcript and nested genes. The recent publication of ENCODE (Encyclopedia of DNA elements) project Consortium, 2007 has prompted many of people involved to proclaim that revolution is underway. The Encode projects is large scale attempt to analyses and annotate the human genome. This is most preferred because these results have been summarized in extra-ordinary complex with massive amount of supplementary material. The Encode proposed some of the criteria to be consider before labelling anything as a gene and ultimately with these criteria some definition are proposed. The summary of proposed definition is concisely summarized as “The gene is a union of genomic sequence encoding a coherent set of potentially overlapping functional products.” However, even this definition has its aspects and implication too (genome.cshlp.org/content/17/6/669.full.pdf).The importance of Encode project is that a significant fraction of human genome has been analyzed in detail (1%) and group made some serious attempts to find out whether transcripts really represent functional RNAs. The ENCODE project works on “extensive transcriptional activity” of genome. An important aspect to proposed definitions is the requirement of protein or RNA product must be functional to be qualified as a particular gene. With this advent of defining the gene the project now seriously move forward from the question of “what is gene”? To “what is function”? The gene now as prescribed as function, however all the function of molecules of all genome is still unknown. The Encode however move ahead from “protein-centric” view of gene to “function-centric” because of some DNA sequence that still transcribe RNAs but not protein (e.g. tRNA and rRNAs). But these both (tRNA and rRNAs) can cause phenotype. CONCLUSIONS:The discussion for the definitions of gene is still going on and looks to continue for coming years as well. The observations summarized above, together with many others, have created the interesting situation that the central term of genetics— “the gene”—can no longer be defined in simple terms.The concrete idea that include and describe for whole organism has not been found yet. All the classical, Neo-classical and modern concept lacks some necessary points but some subtle difference is found in all these definition. The modern concept refers to transcripts as important product but not the protein. What has unchanged is genotype do determine phenotype and by this work of Encode project the works may seem simpler but has added more complexity in further days to come. We are currently left with a rather abstract, open and generalized concept of the gene, even though our comprehension of the structure and organization of the genetic material has greatly increased. So to summarize No definition of gene is still perfect-all of them have exceptions and we need more research and information before accepting any sort of conclusions.   References:·        The ENCODE Project Consortium, 2007Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.·        Jacob F., Monod J., 1961a Genetic regulatory mechanisms in the synthesis of proteins. J. Mol.     Biol. 3: 318–356.·        Keller E. F., 2000The Century of the Gene. Harvard University Press, Cambridge, MA. ·        Pearson H., 2006 What is a gene? Nature 441: 399–401·        Pesole G., 2008What is a gene? An updated operational definition. Gene 417: 1–4.·        Strauss B. S., 2016 Biochemical genetics and molecular biology: the contributions of George Beadle and Edward Tatum. Genetics 203: 13–20·        http://www.jstor.org/stable/2829967·        https://www.ncbi.nlm.nih.gov·        www.natureinstitute.org/pub/ic/ic14/gene.htm    

 

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