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exons & protein domains

Arlin Stoltzfus arlin at is.dal.ca
Fri Jul 19 18:47:03 EST 1996

R M Bernstein wrote:
> hi bob,
> these are theories perhaps suggested by crick himself (prediction of rna
> world and all that it implies), and since championed by gilbert and more
> recently wf doolittle-and others. 
. . . 
> all errors in the story above are open to correction/clarification
> ralph

The history of speculation about introns following their discovery in 1977 
is actually a bit different, and is not so much owing to Crick as implied

1977 - many authors speculate that introns are "good" for something, such as
       chromosome structure or gene regulation.

1978 - Gilbert (Nature 271, 501) gathers together diverse ideas to the effect
       that introns are beneficial and that their "role" is to speed evolution
       by various means including developmental gene rearrangements [this
       is the idea that is now called "exon shuffling"].  

1978 - Darnell (Science 202, 1257) and Doolittle (Nature 272, 581) suggest 
       that split genes might predate eukaryotes, and go even further 
       to suggest that they might represent a primordial form of gene 
       organization that predates even a eukaryote-prokaryote ancestor.

1978 - Blake (Nature 273, 267) suggests that the modularity of split genes may 
       reflect the modularity of proteins, such that ancient exon shuffling may 
       explain such observations as the recurrence a nucleotide-binding module 
       in different (ancient) dehydrogenase enzymes.

1979 - Crick (Science 204, 264) considers quite a wide array of possibilities,
       and makes the novel suggestion that introns may operate similarly to 
       bacterial insertion sequences in creating a small target-site 

Although Crick's paper was arguably the most lucid of these, the priority for 
exon shuffling goes to Gilbert, the priority for introns-early is shared by 
Darnell and Doolittle, and the priority for the idea that exons encode 
structural modules goes to Blake.   It is not clear who gets the priority for
the idea of introns as transposable elements that insert into genes.  Both
Crick and Cavalier-Smith cite their own (separate) papers from 1978 in this
regard, and these are papers I have not yet seen.  

> goal.  functional domains- as defined not only by exons that encode a
> "functional" area of a protein, but that are separated by introns from other
> exons, and not themselves interrupted- do indeed exist

Do exons coincide with some protein domains just by chance, or is there a 
statistically significant correlation?  Does this apply to ancient proteins 
as well as to recently evolved ones?

Arlin Stoltzfus
Department of Biochemistry
Dalhousie University
Halifax, Nova Scotia B3H 4H7 CANADA
(email) arlin at is.dal.ca 
(phone) 902-494-3569 
(fax) 902-494-1355

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