Split gene

R. Breathnach, P. Chambon (1981) Organization and expression of eukaryotic split genes coding for proteins. Armu. Rev. Biochem., 50 349-383... 

Nearly all of the RNA of the cell is synthesized (transcribed) in the nucleus, according to the instructions encoded in the DNA. Some of the RNA then moves out of the nucleus into the cytoplasm where it functions in protein synthesis and in some other ways. Many eukaryotic genes consist of several sequences that may be separated in the DNA of a chromosome by intervening sequences of hundreds or thousands of base pairs. The long RNA transcripts made from these split genes must be cut and spliced in the nucleus to form the correct messenger RNA molecules which are then sent out to the ribosomes in the cytoplasm. 

In this section, we will consider only a few biochemical and other aspects of multicellular animals or Metazoa. The sudden appearance of a large number of Metazoans about 0.5 x 109 years ago113 114 may have been an outcome of the appearance of split genes (see Section B, 1). As a result of gene duplication the coding pieces of split genes, the exons, could be moved to new locations in a chromosome where they could have become fused with other pieces of DNA to form entirely new genes.115... 

Structural domains of proteins are sometimes encoded by a single coding segment of DNA i.e., by a single exon in a split gene. Domains of this type may have served as evolutionarily mobile modules that have spread to new proteins and multiplied during evolution. For example, the immunoglobulin structural domain is found not only in antibodies but also in a variety of cell surface proteins.229 252... 

Richard J. Roberts and Phillip A. Sharp Physiology/Medicine Discovery of split genes... 

More recently, the study of the expression of the wild-type split gene fucAl and of its site-directed mutants in the slippery sequence demonstrated that fucAl is expressed by programmed -1 frameshifting in both E. coli and S. solfataricus. This was the first experimental demonstration that this kind of recoding is present in the Archaea domain of life and, thus, universally conserved [Cobucci-Ponzano et al 2006],... 

The observation of split genes led to the hypothesis that perhaps new proteins could be made by shuffling the DNA fragments of genes that code for parts of old proteins—much as cards can be picked from several piles to give a new arrangement. To support the hypothesis, advocates point to similarities in the amino acid sequences and shapes of discrete portions (called domains) of different proteins. 

This strategy involves splitting gene expression between two or three different loci, usually different plasmids or genomes (Fig. 

P.A. Sharp. 1994. Split genes and RNA splicing Cell 77 805- 815. (PubMed)... 

Since the discovery of split genes it was observed that practically all introns contain two very conservative dinucleotides. The donor site has GT exactly at the intron s 5 -boundary and the acceptor site has AG exactly at its 3 -boundary [6, 7]. We call splice sites of this type canonical. Introns flanked by the standard GT-AG pairs excised from pre-mRNA by the spliceosome including Ul, U2, U4/U6 and U5 snRNPs [7]. Recently, a few examples of a new type of splice pair, a AT-AC, has been discovered. It is processed by a related, but different splicing machinery [8, 9]. AT-AC introns are excised by a novel type of spliceosome composed of snRNPs Ull, U12, U4atac/U6atac, and U5 [10, 11, 12]. Several other cases of non-canonical splice sites with... 

Breathnach R., Chambon P. (1981) Organization and expression eukaryotic of split genes for coding proteins. Annu. 

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