By Levi Clancy for Student Reader on
|Humans||3x109 base pairs||~25,000 genes|
|Fruit fly||1.2x108 base pairs||~13,600 genes|
|Round worm||9.7x107 base pairs||~19,100 genes|
|Bakers yeast||1.2x107 base pairs||~6000 genes|
Does gene number correlate with complexity? As shown in the adjacent table, it obviously does not. Rather, alternative splicing correlates with complexity. 95% of Human genes are known to exhibit alternative splicing. Complex Transcription Units use alternative splicing to produce more than one type of mRNA. Patterns of RNA spliciing can combine to produce a dizzying array of alternatively spliced isoforms.
The Slo or Bk channel has over 500 isoforms.the neurexin protein has 2,346 isoforms; the para-sodium channel has 1,536 isoforms; the Drosophila DSCAM Receptor can potentially be made in 38,016 different spliced isoforms. Somatic sexual development in Drosophila is controlled by a cascade of splicing factors each regulating the splicing of genes downstream in the pathway. And cochlear hair cells are tuned to respond to different frequencies via alternative RNA splicing.
Alternative RNA splicing is an important aspect of gene control in metazoans (multicellular animals). Two general molecular mechanisms can regulate the use of alternative splice sites in complex transcription units: repress exon inclusion (as Sxl does); and promote exon inclusion (as Tra does). Sxl sits on L3 and blocks assembly of spliceosome components, thus causing the entire exon to get skipped. Tra stabilizes the exon recognition complex by binding SR proteins, thus causing an exon to get included that otherwise would not have been.
Sxl sits on L3, forming a functional L1-L2-L4 Sxl protein. This Sxl sits on Tra's 2nd exon and a function Tra protein is expressed composed of Exons 1 and 3. Rbp1 and Tra2 sit at the 5' end of the 4th Dsx exon, promoting splicing at that region and thus inclusion of Exon 4 (to encode a functional Dsx protein).
There are many examples of regulation in mammals where important changes in gene activity are regulated by alternative splicing. These systems use pre-mRNA binding proteins to enhance or repress particular splicing choices. These proteins have different types, numbers, and arrangements of RNA binding domains, and other domains that can be involved in protein/protein interactions.
The RNA binding domains target the proteins to specific short sequence elements adjacent to sites of regulation. Alternative splicing is especially common in the mammalian nervous system, where it is used to diversify many proteins important for neuronal development and function. Small cassette exons create short peptide inserts that determine precise changes in ligand binding, electrophysiology, or subcellular targeting.
|BK Channels||Cochlear cells are tuned use alternative splicing of α subunit exons.|
|Sxl Protein||Drosophila use alternative splicing for sex differentiation via Sxl protein.|