Re: Alternative Splicing

wade wrote:

> Larry Moran wrote:
>
>>On 30 Nov 2005 15:29:33 -0800, wade <wade.hines@xxxxxxx> wrote:
>>
>>[snip]
>>
>>
>>>Clearly, if 10 exons for proteinX are conserved for all studied
>>>vertibrate genomes, suggesting that a splice variant is mostly
>>>unique to one species is dubious. But I do forsee some wonderfull
>>>papers that I hope will soon be published "Most variable splice
>>>claims are bunk". Wish I could take a few months off to do the
>>>work and write it.
>>
>>I'm working on it. I've assembled all of the alternative splice data
>>for human and mouse HSP70 genes. These genes are among the most
>>highly conserved genes known. The predicted splice variants are
>>supposed to produce an abundant array of truncated proteins with
>>various inserts and deletions within the hydrophibic core and around
>>the active sites of the protein.
>>
>>It makes no sense whatsoever that mammalian genomes would produce
>>such strange variants of such highly conserved genes. The HSP70
>>proteins play an important role as essential chaperones in all
>>species. Furthermore, the mouse and human alternatively spiced
>>variants are different. This is silly. It's not possible that
>>humans and mice could have evolved strange variants of these
>>genes in the past 100 million years when their structure was
>>conserved for the previous 3,500 million years.
>>
>>The patterns of alternative splice variants are predicted from the
>>EST data. The genome annotators have ignored this data for the HSP70
>>genes because they know it's an artifact. The patterns are no
>>different than those for all the other genes.
>>
>>Here's an example for HSPA5 (BiP/GRP78).
>>
>>http://spliceinfo.mbc.nctu.edu.tw/ps_splice_view.php?gs_id=ENSG00000044574
>>
>>This leaves us with three possibilities ....
>>
>>1. I've made a serious mistake and the human/mouse HSP70 genes
>> really do produce an abundance of alternatively spliced variants.
>>
>>2. The HSP70 genes are very special. The EST data is no good for
>> those genes but it's perfectly valid for all those other genes
>> with mostly unknown protein products whose structures haven't
>> been solved.
>>
>>3. The entire set of EST data is flawed and other genes are just
>> like the HSP70 genes. They don't have alternatively spliced
>> variants.
>>
>>Wanna help with the paper? :-)
>
>
> There's wanna and there's reality.
>
> I think the thing to turn what you've started into a great paper would
> be to have some solid examples of some proteins that are products
> of variably spliced genes (like where there's legit data for
> functioning
> translation products made of actual amino acids). Observations on
> how real proteins are conserved across species may be lost on the
> vsplice sects but they might resonate with those who occupy an orbit
> somewhat closer to Earth.

I don't know much about this subject, but I can give you one real
alternate-splicing protein both of whose forms have known functions;
well, partly known. It's c-myc. The first exon is usually untranslated,
but in a variant form a short section near the end of the exon is
translated to produce a slightly longer peptide. In the usual form
translation starts at the beginning of the second exon.

The only reason I know any of this is because I'm using c-myc as a
phylogenetic marker.

> I have considered mining some of the proteomics data where there
> are putative MS/MS spectral matches to peptides matching vsplice
> forms of proteins. But then, I have other things to do that I actually
> get paid to do and publications to write on things I've actually done.
> Still, it might help settle a bet.
>

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