Point mutations

Damien Broderick (damien@ariel.ucs.unimelb.edu.au)
Thu, 27 Aug 1998 23:56:38 +0000

I hope you'll all forgive me if I treat the list for a moment as an intellectual resource to be plundered. Specifically, I suddenly realised that there's a bizarre hole right in the middle of my layperson's grasp of elementary molecular biology.

Everyone knows that DNA is prey to mutations, most of them quickly edited out by vigilant repair mechanisms, most of the rest neutral or bad news, only a few improving the genes they happen to occur within. But by what chemical pathway do those mutations come about? I'd always assumed that most of them involved gross *deletions* of one or more nucleotide bases, the implication being that the least dangerous deletion would knock out three adjacent bases in one go (otherwise *all* the subsequent three-letter codons are fouled). However, many mutations occur at a single point. The classic instance is the change creating sickle cell anaemia, in which position 6 in the 146 amino acid chain has valine instead of glutamic acid. Presumably this means that an adenine has been changed into a uracil (or, in the DNA chain, into a thymine).

But how the hell does the equivalent of a random impact do that?

It struck me that this is about as obvious as finding that a WIFE can be mistaken for a HAT. Well, that a WIFE can be turned into a WIG.

I'd like to draw you little pictures of the bases at this point, but it's too hard in email. My point is that this mutation calls for a purine double ring to be changed deftly into a pyramidine single ring, with all manner of small but precise replacements of Ns and Os and Hs. I'm sure such things *can* happen by chance, but it looks as if it would have to be either a cumulative process (ruled out by the way DNA copying occurs, I'd imagine) or a strange event akin to four eccentrically-clad skaters running into each other and rebounding, leaving the guy in the middle dressed in a dinner suit.

Any advice for the perplexed?

Damien Broderick