COMPUTING SCIENCE
Ode to the Code
Brian Hayes
Egged on by Error
Early guesses about the nature of the code often started from an
assumption that it would maximize information density. One
conjecture had each nucleotide base spelling out three messages at
once. The concern with efficiency turned out to be misplaced;
information density is not a very high priority for most organisms.
The concept that has replaced efficiency as the great desideratum in
genetic coding is error-tolerance, or robustness. In one way or
another, the code is thought to minimize the incidence and the
consequences of errors in the transmission of genetic information,
so that meaning can be recovered even from garbled messages.
Among the many ways that genetic signals could go awry, two kinds of
errors have been singled out for attention: mistranslations and
mutations. Errors in translation disrupt the reading of the genetic
message—the flow of information from DNA to RNA and then to
protein—but they leave the DNA itself intact. Translation
errors were probably of great importance early in the history of
life, when the machinery of protein synthesis was imprecise.
Mistranslations are less frequent now, and less harmful. Each error
disables only a single protein molecule. Mutations are another
matter: They alter the DNA, the permanent genetic archive. Whereas a
translation error is like an inkblot marring one copy of a book, a
mutation is a flaw in the printing plate, reproduced in every copy.
The simplest "point" mutations substitute one nucleotide
for another at a single site on the DNA (with a corresponding change
on the opposite strand).
The idea that fault tolerance might shape the genetic code arose as
soon as biologists got their first glimpse of the codon table. The
mapping from codons to amino acids is highly degenerate: In many
cases multiple codons specify the same amino acid. But the
synonymous codons are not just scattered haphazardly across the
table; they clump together. Because of these clusters, a misreading
or mutation has a better-than-average chance of producing a new
codon that still translates into the same amino acid.
Closer examination of the table—with some knowledge of amino
acid chemistry—revealed another possible strategy for coping
with errors. When a change to a single nucleotide does not yield the
same amino acid, it nonetheless has a good chance of producing one
with similar properties. For example, all the codons with a middle
nucleotide of U correspond to amino acids that are hydrophobic, or
water-repellent, a trait governing how the chain of amino acids in a
protein molecule folds up in the aqueous environment of the cell.
Thus at least two-thirds of the time a point mutation in one of
these codons will either leave the identity of the amino acid
unchanged or will substitute another hydrophobic amino acid.
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