Alternative splicing

The alternative splicing (also differential splicing or tissue-specific splicing called ) is a special procedure in the context of transcription in eukaryotes dar. Viruses that infect eukaryotes, use this mechanism. From the same DNA sequence and, accordingly, the same pre-mRNA, several different mature mRNA molecules and their translation through a plurality of different polypeptides or proteins may be formed. About one third of all human genes - some sources even go up to 59 percent off - subject to alternative splicing and dysregulation in this context are common cause of various diseases.

Forms of alternative splicing

In the alternative splicing is decided only during the splicing which RNA sequences are introns and exons that. The regulation is carried out via Splicefaktoren ( proteins that recognize the signals on the selection of RNA and the splice sites influence ). Different forms of alternative splicing can be distinguished:

  • Kassettenexons ( mutually exclusive exons ),
  • Skipping of exons ( exon skipping )
  • Maintaining of introns ( intron retention ) or
  • The use of different 5 'or 3' splice sites ( alternative 5 ' / 3' splice site ), see figure opposite.

Many proteins from a single gene

The discovery of alternative splicing means that the one- gene-one enzyme hypothesis for eukaryotes is not strictly true. A DNA sequence, ie, a gene may encode different proteins. In this way, for example, a human cell able to produce, with around 33,000 genes hundreds of thousands of different proteins - so arises from relatively few genes an extremely complex proteome 500000-1000000 protein species. The information density of DNA is thus significantly increased by superposition.

An extreme example of this: DSCAM, a gene in Drosophila melanogaster that controls the direction of growth of nerve cells, has several Kassettenexons that can be combined, resulting in a calculated total number of 38 016 different proteins from only this results in a gene. However, few of them were actually detected in the organism. In contrast, the number of genes in this organism appears relatively small, with about 18,000. This impressively underlines that the large number of proteins in an organism is not primarily determined by the number of its genes, but rather by the alternative splicing of pre-mRNAs.

Impact on the genetics

The number of human genes remaining after sequencing the genome with approximately 33,000 now far behind the original assumptions. However, since almost every other gene can be alternatively spliced ​​, a much higher variety of proteins can be explained despite the seemingly low number of genes. Therefore, just provides an understanding of alternative splicing, a major challenge in the study of human protein diversity and thus the understanding of many diseases (such as cancer) and hereditary diseases dar.

Splicing and evolution

The alternative splicing represents a particularly significant evolutionary development in eukaryotes is:

  • The appearance of new proteins can be carried out much easier than in prokaryotes, through altered regulation of splicing.
  • The probability that a newly arisen through alternative splicing protein is functional, is higher than that of a resultant by mutating the DNA sequence encoding the novel protein. Each protein produced in this way in the context of evolution contains at least several already functioning in other proteins amino acid sequences.
  • Thus, the adaptation of eukaryotes to changing living conditions is easier and faster. This could have been a crucial step in the evolution of multicellular organisms with longer generation time. While bacteria between two generations often less than an hour goes by, this time can (example man ) grow in eukaryotes several decades. Without an appropriate mechanism for efficient mutations eukaryotes would hardly have been able to adapt to changing environmental conditions.
52712
de