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SPLICING IT UP! Is this the answer to our complexity?

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The Genetic Basis of Stuff and Things

The Genetic Basis of Stuff and Things

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Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. Nat Genet. 2008 Dec;40(12):1413-5. doi: 10.1038/ng.259.
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Have you ever considered the functional complexity of our kind? The human species is incredibly special and indeed a worthwhile puzzle to decode. In 2008 Qun Pan and other researchers investigated the flaws of the popular “one gene - one protein” hypothesis and sought to piece together the mysteries of the human transcriptome. With the new advancements in technology at the time, high throughput sequencing techniques promised the discovery of alternative splicing junctions.
By sequencing human tissues, the splicing junctions and frequency of splicing events occurring was successfully recorded. From the 15,702 genes in six tissues, surveying detected an upper limit of 11,099 new splice junctions. This is a rate of 20% new detection in the multiexon genes. Additionally, 95% of multiexon genes contained at least one alternative splicing event. These numbers are a big deal and reveal not just how far genetic research has come, but importantly the complexity of human multiexon genes. It is simply evidence of the abundance of protein products needed to support all humans, all coded by a compact genome. Not only this but a relationship between the frequency of splicing junctions in a tissue and level of complex tissue function was evident! It’s unsurprising that the brain tissue - with an extremely important job of telling everything in the body what to do - has the highest proportion of splicing to support its sheer complexity. This supports that a deep survey of the human transcriptome and other organisms is another window of opportunity to gain insight into their cellular and overall functional complexity. Further, it allows a range of researchers to approach the ideas of evolution from a different genetic perspective.
Since technology has allowed the scope of genetic research methods to increase, there really is an unimaginable amount of information for us all to discover.
Creator: Grace
References:
Aebersold R, Agar JN, Amster IJ, Baker MS, Bertozzi CR, Boja ES, Costello CE, Cravatt BF, Fenselau C, Garcia BA et al., How many human proteoforms are there? Nat Chem Biol. 2018;14(3):206-214.
Gilbert W. Why genes in pieces? Nature. 1978;271(5645):501.
Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet. 2008;40(12):1413-1415.
Smith CW, Valcárcel J. Alternative pre-mRNA splicing: The logic of combinatorial control. Trends Biochem Sci. 2000;25(8):381-388.
Wang Y, Liu J, Huang B, Xu YM, Li J, Huang LF, Lin J, Zhang J, Min QH, Yang WM et al., Mechanism of alternative splicing and its regulation. Biomed Rep. 2015;3(2):152-158.
Wang Z, Burge CB. Splicing regulation: From a parts list of regulatory elements to an integrated splicing code. RNA. 2008;14(5):802-813.
Will CL, Lührmann R. Spliceosome structure and function. Cold Spring Harb Perspect Biol. 2011;3(7).

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