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I only know splice variants are produced by different combinations of introns and exons. I wish to know why there is a need of such function. Perhaps using the same amount of DNA sequence to produce multiple proteins saves genetic material. Also, I want to know what contribute to the need for splice variants feature (e.g. evolutionary pressure, the need to increase the complexity)

I find that in human, protein CD81 is predicted by Ensembl to have a lot of splice variants (http://grch37.ensembl.org/Homo_sapiens/Gene/Splice?db=core;g=ENSG00000110651;r=11:2398547-2418649;t=ENST00000475945). However, only 1 of them is characterized. Thus, splice variants seem redundant. Any examples of splice variants actually carry different function?

stareagle130
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The reason is very simply to provide enough variation in a limited sized genome to produce the repertoire of proteins produced by the cells of multicellular organisms. It is also a matter of efficiency and reduced energy consumption.

Consider that on average there are about 100,000 unique protein types being produced in a human cell [1], but the human genome is estimated to contain only 19,042 protein coding genes [2], then the cell needs some way to vary that limited instruction set.

Also remember that differentiated cell types express certain genes but not others, and produce different proteins that other cells do. So that implies that there are more than 100,000 different types of human proteins, and far fewer than 19,042 genes being expressed in any one cell at the same time.

So without splice variants, our genomes would either need to be far larger than the approximately 3 billion base pairs it is already or our repertoire of proteins would be significantly less. We would also have a lot of redundancy, as many common exons would have to be repeated over an over again. That would require a lot more energy for DNA synthesis, and nucleic acid synthesis, etc. The process would become inefficient rather quickly and would likely make complex multicellular animal life untenable.

There is a bit of an error in your question. Splice variants are identified by the mRNAs that are produced, and exons are defined by the sequence that is in the mature mRNA. Introns are, by definition spliced out of the pre-mRNA, meaning that splice variants are not "produced by different combinations of introns and exons." Splice variants will only consist of different combinations of exons. The only time an intron would be found in a mature mRNA is if a splice site is mutated and it is no longer recognized by the spliceosome, so it leaves the intron in incorrectly. This will generally result in a non functional protein.

EDIT

The collection of components required to carry out the intricate processes involved in generating and maintaining a living, breathing and, sometimes, thinking organism is staggeringly complex. Where do all of the parts come from? Early estimates stated that about 100,000 genes would be required to make up a mammal; however, the actual number is less than one-quarter of that, barely four times the number of genes in budding yeast. It is now clear that the 'missing' information is in large part provided by alternative splicing, the process by which multiple different functional messenger RNAs, and therefore proteins, can be synthesized from a single gene.

-Expansion of the eukaryotic proteome by alternative splicing: Nilsen and Graveley

Alternative splicing of pre‐messenger ribonucleic acid (pre‐mRNA) allows the generation of different mRNAs from the same gene. Evolution of alternative splicing affecting translated regions of mRNAs permits the synthesis of different proteins from a single gene, significantly increasing the diversity of the protein repertoire.

-Patthy, László(Apr 2008) Alternative Splicing: Evolution. In: eLS. John Wiley & Sons Ltd, Chichester.

Also while I am not one to accept a Nobel Prize at face value, they are usually awarded when the field accepts the explanation of the hypothesis. The 1993 Nobel Prize in Physiology and Medicine was awarded to Richard J. Roberts and Phillip A. Sharp "for their discovery of 'split genes'."

AMR
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  • Thanks AMR! Do you know any sources to back the argument? I feel like the answer is rather a deduction from the two cited numbers. Or the deduction you gave is widely accepted? – stareagle130 Oct 23 '15 at 01:38
  • You cannot escape the deduction, but it is pretty much universally accepted. – AMR Oct 23 '15 at 02:10
  • An interesting application of splicing is in CD45 on T cells. Essentially, effector and memory T cells express a splice variant that is shorter than the CD45 expressed by naive T cells, and it facilitates faster TCR signalling. The splice mechanisms that catalyze this variant are activated during the effector/memory state. In this case we're not trying to fit more genes into less DNA, we're actually increasing efficiency of a system! [Some light reading on CD45.](http://www.nature.com/icb/journal/v75/n5/pdf/icb199768a.pdf) – CKM Oct 24 '15 at 00:04
  • @Kendall, I am not sure I see your point? The entire pre-mRNA of the gene encoding CD45 will be transcribed. The regulation of splicing determines the isoform that the cell expresses and significantly increases the probability of that isoform, but does not change the fact that there are several possible isoforms present on the on the pre-mRNA to chose from. That the isoform expressed is more efficient is a function of the conformation of the molecule that alternate splicing choses. No? Somatic recombination of BCRs and TCRs are more in line with what I think you are trying to point out. – AMR Oct 24 '15 at 00:19
  • There was no point other than an example of utility, but if that was a poor example I apologize! – CKM Oct 24 '15 at 00:38
  • @Kendall Not a poor example, just an example of regulated alternative splicing, which is something I did not address in my answer. That is probably worthy of an answer of its own if you are up for it. – AMR Oct 24 '15 at 00:42
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Insofar organismal complexity is defined as the number of known cell types, there is a strong relationship between splicing, the repertoire of isoforms and organismal complexity.

See paper here

Ankur Chakravarthy
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  • I personally think that you embark up a slippery slope when you try to qualify or quantify organismal complexity. It is only a veiled attempt at trying to justify ones place in an arbitrary hierarchy of living things. More important than complexity is the study of homology, as it gives us insight into processes and allows us to test hypotheses without having to rely on empiricism. If we can amass evidence by studying flies or worms or yeast that can be translated to humans, then all the better, as the costs are far lower and the time to obtain results is far less. – AMR Oct 24 '15 at 00:34
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Also, I want to know what contribute to the need for splice variants feature.

One common function of splice variants no one mentioned is to function as a dominant negative of a longer functional full length transcript. dominant negative splice variants So it allows for additional regulation of post-transcriptional processing.

This is actually quite a common function of splice variants.

In addition, as others have mentioned, it adds complexity at a reduced cost. Many transcription factor proteins have both transactivation domains (ability to interact with and regulate DNA transcription) and protein-protein interacting domains. With splicing variants, the organism can make different parts of that protein that are functional for only one subset of activity.

akaDrHouse
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