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Index >> Genes >> Genes With in Genes (Overlapping Genes)

Genes With in Genes (Overlapping Genes)

Genes With in Genes (Overlapping Genes)
According to one of the dogmas of the genetic code each gene is responsible for the coding of one protein/polypeptide.

This hypothesis was proposed by Beadle and Tatum in the 1940s and is called the one gene, one protein hypothesis. Barrell and his coworkers (1976) first gave evidence that suggests the possibility of overlapping of genes in the bacterial virus φ X I74.

The bacteriophage consists of an icosahedral protein capsid containing single-stranded circular DNA. Genetic mapping techniques have shown that the bacteriophage has 9 genes (arranged in the order A-B-C-D-E-J-F-G-H) which code for 9 proteins.

The functions of these genes is as follows:
Gene A- DNA replication.
Genes Band D- assembly of phage particle,
Gene C- function not known.
Genes F, G and H- for structural capsid proteins.

Barrell et at presented evidence that the proteins coded by genes D and, E are specified by the same segment of DNA.

The genetic code assumes the coding of each amino acid unit of the protein molecule by a codon of three nucleotides (triplet).

In almost all organisms the total length of the DNA molecule available for coding proteins exceeds the total length of the protein product. In the phage φXI74, however, the total length of the proteins coded is more than the length of the DNA coding it.

Sanger and his colleagues (1976, 1977) have mapped the entire nucleotide sequence of φX174 DNA and phage G4 DNA.φX174 DNA contains 5,386 nucleotides. On the basis of the triplet code this number should code for a maximum of about 1,800 amino acids having a total weight of about 200,000 daltons.

Actually, however, the total proteins coded have a molecular weight of 250,000 daltons. The phage DNA which should have a coding capacity of 5 to 6 average sized protein molecules actually codes for 9 proteins. The virus DNA is thus apparently 10 to 15% too short for the total proteins coded.

A comparison of the DNA base sequence with the amino acid sequences of the proteins coded revealed that in two cases the same gene coded for two different proteins.

Thus two genes which should normally have coded two proteins actually coded four. Sanger and his coworkers found that gene B (360 nucleotides) was completely contained within gene A (1536 nucleotides). Similarly, gene E (273 nucleotides) was contained in gene D (1456 nucleotides).

The protein synthesized by gene B is not simply a shorter version of that synthesized by gene A. The two proteins have completely different amino acid sequences. Similarly with the proteins synthesized by genes D and E. It has been explained that the coding of two proteins by one gene is achieved by a shift in frame reading.

For example, a reading frame of..............G,AAG,TTA,ACA............... nucleotides codes for the amino acids lysine, leucine and threonine. If the frame is read from one point earlier it becomes GAA,GTT,AAC,A..which codes for glutamine, valine and asparagine.

Thus, the same gene can code for two different sequences by a frame shift (overlapping code) and produce two totally different proteins. Since one gene codes for more than one protein an amendment to the one-gene, one-protein dogma becomes necessary, at least in a few cases like ØX174 and G4.

Another interesting fact is that the termination codon of gene D and the intitation codon of gene J overlap by one nucleotide
- -- T-A-A-T-G--­
The bacteriophage G4, which infects E; coli, also has overlapping genes. Gene B is completely contained within gene. A and gene E within gene D. Gene K is made up of the last 86 nucleotides of gene A and the first 89 nucleotides of gene C.

The condition of overlapping genes is not of common occurrence. It may have arisen in the smaller viruses because of the limitations of the quantity of DNA that can be enclosed in the small viral capsides.

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