In 1940, Beadle and Tatum proposed one-gene –one protein hypothesis which explains that one gene encodes for one protein. However, If one gene consists of 1,500 base pair, a protein of 500 amino acids in length would be synthesized. In addition, if the same sequence read in two different ways, two different amino acid would be synthesized by the same sequence of base pair. It means, the same DNA sequence can be synthesized more than one protein at different time. It was realised for the first time when the total number of protein synthesized by ÆX174 exceeded from the coding potential of the phage genome. A similar phenomenon is found in the tumour virus SV40 where the total molecular weight of protein (i.e. VP1, VP2, and VP3) synthesized by SV40 gene is much more than the size of the DNA molecule (5,200 base pair i.e. 1,733 codons). Form this observation concept of overlapping gene has emerged.
For the first time B.G. Barrell and co-workers in 1970 gave the evidence for the possibility of the above fact based on the overlapping genes found in bacteriophage ÆX174. This virus contains an icosahedral capsid with the knob of each vertex enclosing the single stranded circular DNA (fig). F.Sanger and co-workers in1977 mapped the whole nucleoside sequence of phage ÆX174, and phage G4 DNA. The sequence of genes D, E and J, and B, to overlapping in the whole sequence of ÆX174.
The ÆX174 strand is made up of 5,386 nucleotide of known base sequences. If a single reading frame was used, about 1,795 amino acid would be encoded in the sequence and with and average protein size of about 400 amino acids, only 3-5 proteins could be made. In contrast, ÆX174 makes 11 proteins containing of total more than 2,300 amino acids. The sequence of gene A is now known to contain all of gene B. Gene B is translated during a different reading frame from gene A. similarly gene E is encoded within gene D. Another translational control mechanism expand the use of gene A. The 37 k Dalton gene A* protein is found by reinitiating translation at an internal AUG codon within gene A message. The two translational proteins are synthesized by the same translational phase but the function of two proteins differ. Protein K initiated near the end of gene A, includes the base sequence of gene B, and terminates in gene C. For example, a reading frame of …… G,AAG,TTA,ACA…… nucleotides encodes the amino acid lysine, leucine and threonine. However, after reading the frame one nucleotide earlier, the codes become... GAA,GTT,AAC,A…. that encode glutamine, valine and asparagines, respectively.
It is obvious that by shifting the reading frame i.e. overlapping the code, the same gene can codes two different proteins. Similarly, in the nucleotide sequence …. TAATG…., TAA act as termination code of gene D, and ATG acts as initiation code of gene J. Here the nucleotide ‘A’ between A and T overlaps between the two codes. Therefore, the amino acid sequence of A* similar to the segment of protein A. In addition, overlapping genes have also been detected in animal virus SV40, and tryptophan mRNA of E.Coli.
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