COMPUTING SCIENCE
Ode to the Code
Brian Hayes
Code On, Codon
Solomon W. Golomb of the University of Southern California, who was
a central figure in the first round of speculations about the
genetic code, has summed up the spirit of that era: The approach
taken in those days was to ask, "How would Nature have done it,
if she were as clever as I?" Now that we know how nature has
done it, you might think that the period of freewheeling conjecture
would be over, but I am pleased to report that there is no lack of
adventurous ideas about patterns and structures in the genetic code.
Here are just a few of the ideas in circulation.
One of the themes of the earlier period was the need to find some
compelling relation between the numbers 64 and 20. And this quest
had spectacular successes: In at least two schemes, the 64 codons
could specify exactly 20 amino acids, neither more nor less. The
mathematics was so beautiful, it was hard to believe nature would
pass up an opportunity to make use of it. Pierre Béland and
T. F. H. Allen of the St. Lawrence National Institute of
Ecotoxicology in Montreal argue that nature did not miss
the opportunity. They propose a primordial genetic code in which
information was read from both strands of the DNA at once, and all
messages were palindromic, so that they could be read in either
direction. Under these conditions, meaning can be assigned to only
20 of the 64 triplets.
A double-stranded translation system may sound outlandish, and yet
there are hints that the "antisense" strand of DNA may be
more than just a placeholder. Jaromir Konecny, Michael
Schöniger and G. Ludwig Hofacker of the Technical University of
Munich point out that a rough symmetry of the genetic code creates a
kind of antigene opposite every normal gene. Wherever the sense
strand calls for a hydrophilic amino acid, the antisense strand
(read in the opposite direction) is likely to code for a hydrophobic
one. It's even possible that some of these antisense pseudogenes are
transcribed in vivo. William F. Pendergraft III and six
colleagues at the University of North Carolina at Chapel Hill have
recently detected immunological reactions to one such antisense protein.
More generally, there is growing recognition that the genetic code
may encompass more information than just the simple mapping from
codons to amino acids. Synonymous codons may not always be
completely equivalent. It's certainly true that codon frequencies
are not random or uniform. Among the several codons that specify a
given amino acid, some may be common and some rare, and these usage
biases can vary both within and between genomes. The biases probably
help to regulate the rate of protein synthesis: If the transfer RNA
that matches a codon is rare, then transcription of genes including
that codon will be slowed. For some proteins there is evidence that
such pace-setting codons help ensure correct folding of the amino
acid chain.
Another fertile area is the search for symmetries and patterns in
the genetic code. The standard table of codon assignments derives
from the obvious representation of the triplet code as a
4×4×4 cube. Several authors, observing that 64 is equal
not only to 43 but also to 26, suggest
organizing the codon table as a six-dimensional (2x2x2x2x2x2)
hypercube. A mutation is a movement from one vertex to an adjacent
vertex in this structure. The geometry is intriguing, and there are
interesting connections with Gray codes and even with the I
Ching, but I'm not so sure that biologists will find the
concept useful.
Not every interesting idea takes the form of a paper in the
Journal of Theoretical Biology. Another quite different
geometrical interpretation of the genetic code has been presented to
the world in the form of a design for a toy. Mark White, a physician
and inventor in Bloomington, Indiana, discovered that the genetic
code can be represented succinctly on a dodecahedron (a solid whose
surface consists of 12 pentagons) or its dual the icosahedron (made
up of 20 triangles). Each face of the dodecahedron is labeled with
one of the four nucleotides, each of which appears three times. Any
grouping of three adjacent faces, read in the right order, generates
the appropriate amino acid. White has made prototypes of toys that
incorporate this design. He observes that the icosahedral model is
closely related to the very first proposal for a triplet genetic
code, the "diamond code" devised in 1955 by George Gamow.
This neatly closes the circle and takes us back to the beginning of
the story.
© Brian Hayes
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