Linguistics, Semiotics, and Philosophy - Molecular Theory of the Living Cell - page 168

Table 6.6 The principles of the arbitrariness of molecular signs, rule-governed creativity, and
constrained freedom in action at various levels of living systems

Object/function (creativity,
freedom) Levels Sign (rule, constraints)

1. Molecules (a) Protein folding Amino acid sequences 3-D shapes or folds

(b) Catalysis Protein shape Chemical reaction catalyzed

(c) Allostery Allosteric ligand Chemical reaction regulated

(d) Binding Transcription factor Structural genes expressed

2. Cell-extracellular interactions Intercellular messengers Signal transduction pathways

3. Cell-intracellular interactions Genome Morphology, physiology

The arbitrary relation between amino acid sequence and the 3-D shape of a
protein (see Row 1a in Table 6.6 ), which in turn determines its function, has
already been pointed out in Tables 6.1 and 6.2 and is further discussed in Sect.
11.1 . But protein folds are not entirely independent of amino acid sequences or
completely dependent on them either, which may therefore be more accurately
described as “quasi-deterministic” (Ji et al. 2009b). Although point mutations
have been demonstrated to alter the shapes and functions of some proteins (but not
all), it has also been found that an identical amino acid sequence can lead to more
than one dominant conformations or folds, depending on the environmental
conditions under which proteins fold. In fact, the Anfinsen's classic experiments
with ribonuclease A carried out in 1954 clearly demonstrate how sensitively
dependent ribonuclease A conformations are on the environmental conditions
under which it folded. The refolding of the denatured ribonuclease A induced by
the removal of urea followed by the removal of 2-mercaptoethanol led to the
native conformation of the enzyme with the 100% recovery of its enzymic activity
but, when the refolding was induced by removing the denaturants in the reverse
order, that is, removing 2-mercaptoethanol first followed by the removal of urea,
the enzyme folded into nonnative conformations with only 1% of its enzymic
activity recovered. Thus, the Anfinsen experiment of 1954 supports the notion
that conformations of proteins are the functions of both (1) aminoacidsequences
and (2) the environmental conditions under which proteins fold. These dual
conditions for protein folding constitute the core of the unpredictability of the
3-D protein folds (U3DPF) (see Statement 6.1). Thus the principle of arbitrariness
of molecular signs (PAMS), Statement 6.17, may best regarded as reflecting an
aspect of the molecular version of the principle of rule-governed creativity
( RGC ), another of the 13 design features of human language (Hockett 1960).
RGC states that native speakers are able to produce an indefinitely large number
of novel sentences based on finite sets of words and grammatical (or syntactic)
rules and that these sentences can be understood by others in the linguistic
community even though they never encountered them before (Lyons 1992,