May 8, 2007 | David F. Coppedge

New Theory for Introns: Mutation Sponges

When you don’t know where damage will occur, it makes sense to spread the assets around.  Scientists from City of Hope Medical Center (a cancer care and research institute) have a new idea about introns, those regions of DNA “junk“ between the more interesting exons (parts of genes).  Perhaps the introns are mutation sponges.
    Writing in PNAS,1 nine scientists provided evidence that mutations occasionally come in showers.  When a bad translation machine comes along, for instance, it could inflict a lot of damage in a small region.  By spreading the genetic material apart with introns, most of the damage will be absorbed by the non-coding DNA.  Here’s how they expressed it:

The observed mutation showers often will affect one or a few genes in mammalian genomes, because they tend to diminish within 30 kb.  Therefore, most mammalian genes range from 20 kb to 1 Mb with 90+% of the sequence within introns.  Approximately 90% of the mutations within a mutation shower generally would not have functional consequences.  Thus, the introns serve as a “sponge” to absorb many of the mutation showers without damage to protein function.

They also suggested that a mutation shower in the wrong place might produce “cancer in an instant.”  They asked,

Might there be scattered mutation showers throughout the genome that occur, perhaps by nucleotide pool imbalances during replication or another cellular metabolic process?  This is a critical unanswered question.  If scattered mutation showers occur, multiple genes could be inactivated, leading to cancer in an instant.

They said this might explain why many tumors have high averages of mutations.

1Wang, Gonzalez, Scaringe, Tsai, Liu, Gu, Li, Hill and Sommer, “Evidence for mutation showers,” Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0610902104, published online before print May 7, 2007.

No one knows if this is “the reason” for introns, but it shows that there are creative ways to discover a function for something that otherwise looks meaningless.  What a novel concept: sponges in the genome to absorb mutations.  If introns are more likely to take the hits, then the sponges can be cut out after the translation by the spliceosome, and 90% of the errors can be thrown away.  This way, it is more likely the exons will link up without loss of function.  Post-translational proofreading can then provide additional protection against the remaining 10%.  It sounds like an intelligently planned strategy the military or an IT company would use.  Perhaps other functions for introns will come to light if scientists approach them from a design perspective.
    The paper, however, was categorized under the topic of evolution.  The authors said the existence of mutation showers has “implications… for evolution.”  But they did not provide any evidence that mutation showers could advance evolution in any way, shape or form.  Mutation showers cannot be sources of evolutionary innovation.  On the contrary, they are threats to be mitigated.  Risk management requires a strategy appropriate to the threat.  Like Kansas towns in tornado alley, it’s best if they are kept small and separated by large tracts of vacant land.  Such a strategy does not eliminate the threat; it just limits the exposure.
    Yes, this has implications for evolution, but evolutionary progress has nothing to do with it.  This is disaster preparedness, not innovation.  It wouldn’t make any sense to expect to find new functioning towns in the debris of a passing F5 twister – or Boeing 747s, either.  Just ask the folks in Greensburg, Kansas.

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Categories: Genetics

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