The (i) Two research groups separately headed by

The discovery of split genes was made in 1977 by several groups in a variety of materials, which included the (i) Two research groups separately headed by Phillip A. Sharp and Richard J. Roberts studied genes of adenovirus 2.

(ii) Research groups of D.S. Hogness, I.B. David and N. Davidson studied genes for 28S rRNA in Drosophila. (iii) Research groups of P.

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Chambon, P. Leder and R. A. Flavell studied 6 globin genes, ovalbumin genes and tRNA genes. In all these cases the genes were found to be interrupted by intervening sequences. The credit for discovery of split genes, however, goes to Phillip Sharp and Richard Roberts, who won the 1993 Nobel Prize for medicine for their work on split genes. They analyzed the hybrids of late mRNA of adenovirus 2 with the adenovirus ge­nomic DNA. When these mRNA-DNA hybrids were examined under electron microscope, the adjoining sequences of mRNA were found to hybridize with discontinuous stretches of genomic DNA of adenovirus 2.

The intervening DNA sequences were ob­served as loops and the phenomenon was later described as R looping. Chambon’s group compiled sequences of the boundaries of introns from a large number of protein coding eukaryotic genes (not ribosomal RNA or tRNA genes), which revealed the presence of consensus sequences at the intron-exon junctions. These GT was always found at the 5? side of the intron (left splice junction) and AG at the 3? side (right splice junction). This became popu­larly known as GT-AG or Chambon’s rule. Some of the diseases (e.

g. thalassemias) are caused by mutations, which created or abolished these splice junctions. Phillip Sharp’s group and other groups later also conducted studies to elucidate the mechanisms of splicing.

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