Richard J. Roberts and Phillip A. Sharp (1993 Nobel Prize) made their amazing discovery of the existence of split genes in the adenovirus, when they examined a hybridized nucleic acid molecule made between a adenoviral mRNA and its template DNA in the electron microscope. They observed that the mRNA was much shorter in length and thus was not encoded as an equal colinear segment of the DNA molecule (see below). Instead, large loops of unhybridized DNA (A, B and C in figure) were seen. Their interpretation was that the mature messenger RNA was derived from four discountinuous segments on the viral DNA. The segments retained in the mRNA they called EXONS and the intervening sequences (A, B and C), which are excised during mRNA processing and maturation, are called INTRONS.

      mRNA-ssDNA hybridization split genes
  showed that the primary transcript & mRNA
 were not the same size
                                           a DNA Gene is longer than its functional mRNA










Alternative Splicing:

A percursor-mRNA may often be processed into a matured mRNAs with alternative structures. An example where alternative splicing has a dramatic consequence is in somatic sex determination in the fruit fly Drosophila melanogaster.

In this system, the female-specific sxl-protein is a key regulator. It controls a cascade of alternative RNA splicing decisions that finally result in female flies.

   Sex in Drosophila is thus largely determined by
   alternative splicing of mRNA of sxl-protein.

  Other examples :     Thalassemia               Tropomyosin.           back to Molecular Genetics