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  Topic: The Origin of "Information" via natural causes, Refuting a key ID claim (refs, webpages)< Next Oldest | Next Newest >  

Posts: 97
Joined: May 2002

(Permalink) Posted: June 17 2003,14:41   

Retrotransposable, non-coding Alu elements being turned into protein coding exons.  Pretty cool.  

Science. 2003 May 23;300(5623):1288-91.

The birth of an alternatively spliced exon: 3' splice-site selection in Alu exons.

Lev-Maor G, Sorek R, Shomron N, Ast G.

Alu repetitive elements can be inserted into mature messenger RNAs via a splicing-mediated process termed exonization. To understand the molecular basis and the regulation of the process of turning intronic Alus into new exons, we compiled and analyzed a data set of human exonized Alus. We revealed a mechanism that governs 3' splice-site selection in these exons during alternative splicing. On the basis of these findings, we identified mutations that activated the exonization of a silent intronic Alu.

About 5% of alternatively spliced internal exons lead with an Alu sequence, which makes this a fairly common method of creating new "information".  

Here's a excerpt from the commentary that appears in the issue:

It appears that in addition to the distance between two AG dinucleotides, a nucleotide immediatesly upstream of proximal AG is also important.  Hence, a proximal GAG sequence serves as a signal weak enough to create an alternatively spliced Alu exon.  Any mutation of a proximal GAG in the first position results in a constitutive Alu exon.  This is an important observation, because most of the more than 1 million Alu elements in the human genome contain such a potential 3' splice site.  Of these, 238,000 are located within introns of protein-coding genes, and each one can become an exon.  Unfortunately, most mutations will lead to abnormal proteins and are likely to result in disease.  Yet a a small number may create an evolutionary novelty, and nature's "alternative splicing approach" guarantees that such a novelty may be tested while the original protein stays intact.

Another way to exploit an evolutionary novelty without disturbing the function of the original protein is gene duplication (see the figure.)  Gene duplication is one of the major ways in which organisms can generate new genes.  After a gene duplicates, one copy maintains its original function while the other is free to evolve and can be used for "nature's experiments."  Usually, this is accomplished through point mutations and the whole process is very slow.  However, recycling some modules that already exist in a genome (for example, in transposons) can speed up the natural mutagenesis process tremendously.  Several years ago, Iwashita and colleagues discovered a bovine gene containing a piece of a transposable element (called a TE-cassette) in the middle of its open reading-frame.  This cassette contributes a whole new domain to the bovine BCNT protein, namely an endonuclease domain native to the ruminant retrotransposable element-1 (RTE-1).

[Skip stuff about how BCNT is the result of a gene duplication.]

The reports by Lev-Maor et al. and Iwashita and collegues describe different ways in which genes can be rapidly rearranged and acquire evolutionary novelty through the use of so-called junk DNA. These discoveries wouldn't be so exciting if they didn't show how genomes achieve this wihtout disturbing an original protein.  To quote an old Polish proverb: "A wolf is sated and a lamb survived."

The Iwashita paper is still in press, to be published in Molecular Biology and Evolution.  Will be posted here when it's available on PubMed.  :D  


Edited by theyeti on June 17 2003,14:45

  42 replies since May 30 2002,00:02 < Next Oldest | Next Newest >  

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