Tuesday, November 25, 2008

Evil Triplet Repeats and The Age of Magic

I'm not really much of a superhero comic book fan. Ask me whether I prefer the DC Universe or the Marvel Universe, and my answer is pretty much "who cares?" That isn't to say that I don't enjoy comics or other sequential art, though. For example, I love many of the titles in the Vertigo line of graphic novels1.

I've been slowly working my way through the Books of Magic and related titles, which follow the adventures and trials of Timothy Hunter. Tim is a bit of a misfit teenager who learns that he is destined to be the most powerful magician of our age, and his story is about learning the ways of magic, while searching for the truth about his parents and learning to understand himself. While there are some superficial similarities to Harry Potter (which was published several years after the original Books of Magic series), I think the story of Timothy Hunter is much darker and much more wide-ranging, since Tim has to not only learn to navigate the good and evil of the magical world, but also the mundane world of his family and friends.

While the series is fantasy, it has occasionally included tropes that would be familiar to any science fiction fan, including time travel, alternate universes, and a steampunk cyborg. That's why it didn't surprise me that DNA sequencing, genomics and genetic engineering made it's way into the Timothy Hunter mythos.

In issues 8-11 of Hunter: The Age of Magic, genetics and magic become entwined. Tim meets a molecular biologist who has been studying the genomic sequence of evil individuals, including a young girl who became evil - and whose genome changes - when she was possessed by a demon. He discovers that sociopathic behavior is associated with an alteration of the "F5412 Gene".2 In evil individuals the gene has the repeated insertion of three nucleotides in the sequence ACT.

While I wouldn't call triplet DNA repeats evil, they can cause serious problems in the human genome. A few examples of human genetic syndromes caused by trinucleotide repeat insertions:
  • Fragile X syndrome is associated with CGG repeats in the FMR1 gene on the X chromosome. Proper FMR1 expression is required for normal neural development, and excess CGG repeats causes the DNA to be methylated, which silences FMR1 expression. The result is intellectual and physical disability.
  • Huntington's chorea is caused by excess CAG repeats in the Huntingtin gene on chromosome 4. The symptoms include jerky, uncontrollable movements and impaired cognitive abilities, which usually appear when the person carrying the mutation is in her 30s or 40s.
  • Myotonic dystrophy, a muscle wasting disease, can be caused by expansion of the sequence ACG in the DMPK gene on chromosome 19.
The trinucleotide repeats undergo dynamic mutation. Not so much over the course of a liftime, as in the case of a demon possessed little girl, but over the course of multiple generations. The severity of the symptoms can increase as the number of trinucleotide repeats increases from generation to generation. In adult-onset diseases like Huntington's, that means parents can pass a more detrimental form of the mutation on to their children even before they know they are affected themselves. That's a terrible situation, but certainly not evil.

Of course Age of Magic is fantasy, so DNA sequences have the same kind of transformative power as magical words. An analysis of Tim's DNA turns up a sequence with totally different properties that reflect the magic within him. And the DNA from an angel's feather is something else altogether . . .

If you'd like a glimpse of the series, you can download Issue #1 of the Books of Magic

Related reading: Sutherland GR and Richards RI. "Simple tandem DNA repeats and human genetic disease" Proc Natl Acad Sci U S A. 1995 April 25; 92(9): 3636–3641.

1. Yes, I know Vertigo is a DC imprint, but that doesn't mean the graphic novels they produce are exactly part of the DC universe the way the superhero comics are.

2. F5412 appears to be an entirely made up gene on human chromosome 2

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