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one gene one protein dogma no longer true


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It was recently published in March edition's Scientific American. It seems that one gene can infact code for many many proteins, (sometimes up to 6+), this is mainly due to a different perspective on gene expression. Where introns are infact quite important after all, even though they are not "expressed" they play a crucial role in gene expression and protein synthesis.

 

But what are the factors that tell genes to code one protein and not the other? I'm guessing environmental and the body's regulatory mechanisms as of right now.

 

 

(anyways, i'm a bio-chem newb :confused: , if anyone can add/explain more to it it'd be great)

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Well It's now well know that genes can be spliced with different combinations of exons to different mRNA's. Actually most of the diversity between us and other mammals results not so much from having different genes but from having different splicing arrangements on the genes we share.

I'm not sure how they see intron influence as being a stronger case for more then one protein then alternative splicing arrangements. Maybe the mean that it's thought that introns play a large role in regulating how exons are combined? Or the somehow lead to different post translational modifications?

It's be really nice if you could supply a link or reference at least for that article. :)

 

What factors, well you could devide the factors into two types environmental meaning anything coming from outside of the cell and the cells own internal programming. During development when your cells differentiate from stem cells they are giving specific tasks and programs. These cause them to splice mRNA differently, as well as other things.

 

I'm pretty sure patterns of methylation are the main factor.. but I'm really tired now and I'll get my sleep and post when I can think/remmeber properly.

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The record for the largest number of possible proteins (so far) is the gene Dscam from Drosophila with an astonishing 38,016 isoforms!. Dscam is a neuronal protein and interestingly each form binds best to it's identical counterpart allowing for an enormous connections to be specified.

 

 

 

Neuron. 2004 Oct 14;44(2):219-22. Generation of recognition diversity in the nervous system. Schmucker D, Flanagan JG.

 

Cell. 2004 Sep 3;118(5):619-33. Alternative splicing of Drosophila Dscam generates axon guidance receptors that exhibit isoform-specific homophilic binding. Wojtowicz WM, Flanagan JJ, Millard SS, Zipursky SL, Clemens JC.

 

Neuron. 2004 Sep 2;43(5):673-86. Analysis of Dscam diversity in regulating axon guidance in Drosophila mushroom bodies. Zhan XL, Clemens JC, Neves G, Hattori D, Flanagan JJ, Hummel T, Vasconcelos ML, Chess A, Zipursky SL.

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Okay seems no one has actionally answered the original question of what factors are involved.

 

Here is a simplified version of alternative splicing. Basically there is a site (adenine residue) in every intron where a loop forms making the intron into a structure called a lariat. This lariat is then released and degraded bringing the adjacent introns together. Now if you were to coverup one of these sites the other end of the loop would have nowhere to connect to so instead it connects to the site on the next adjacent intron. Now since there is an exon between these two introns this exon would end up being part of the loop on the lariat. So when the lariat is released and the the adjacent exons bind you loose one exon in the lariat.

 

So possible factors could be anything that signals a protein or RNA to cover up this site.

 

Now if the cell covers up different sites and cuts them in different orders you can get a huge varient of products.

 

Now the process is far more complicated than this. (as is everything to do with Eukaryotes) But that's the gist of one mechanism.

 

There are also two other mechanism I can think of that give alternative gene products. I wont go into detail in these since well I don't know them too well.

Both of these aren't know to occur is animals.

 

Trans-splicing occurs in some organisms and involves two different genes splicing togething to give multiple products at the same time.

 

Transcript editing is another process that occurs primarily in some mitochondria and chloroplasts where a Guide RNA is used as a template to introduce U residues into mRNA.

 

 

Now all of this is pretty standard knowledge that can be found in almost any good latest edition molecular biology textbook. So I'm unsure why the new scientist article is title "one gene one protein dogma no longer true" All this has been know for about half decade now.

Maybe I'll dig up the article later. The abstract isn't very specific

 

It really is truely amazing how you can have a few genes coding for factors that recursively allow them to code for far more.

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