The evolutionary forces that produced the canonical genetic code before the
last universal ancestor remain obscure. One hypothesis is that the arrange
ment of amino acid/codon assignments results from selection to minimize the
effects of errors (e.g., mistranslation and mutation) on resulting protein
s. If amino acid similarity is measured as polarity, the canonical code doe
s indeed outperform most theoretical alternatives. However, this finding do
es not hold for other amino acid properties, ignores plausible restrictions
on possible code structure, and does not address the naturally occurring n
onstandard genetic codes. Finally, other analyses have shown that significa
ntly better code structures are possible. Here, we show that if theoretical
ly possible code structures are limited to reflect plausible biological con
straints, and amino acid similarity is quantified using empirical data of s
ubstitution frequencies, the canonical code is at or very close to a global
optimum for error minimization across plausible parameter space. This resu
lt is robust to variation in the methods and assumptions of the analysis. A
lthough significantly better codes do exist under some assumptions, they ar
e extremely rare and thus consistent with reports of an adaptive code: prev
ious analyses which suggest otherwise derive from a misleading metric. Howe
ver, all extant, naturally occurring, secondarily derived, nonstandard gene
tic codes do appear less adaptive. The arrangement of amino acid assignment
s to the codons of the standard genetic code appears to be a direct product
of natural selection for a system that minimizes the phenotypic impact of
genetic error. Potential criticisms of previous analyses appear to be witho
ut substance. That known variants of the standard genetic code appear less
adaptive suggests that different evolutionary factors predominated before a
nd after fixation of the canonical code. While the evidence for an adaptive
code is clear, the process by which the code achieved this optimization re
quires further attention.