Clas Blomberg - Physics of life-Elsevier Science (2007)

338 Part VIII. Applications
one per 3000 (see Loftfield, 1963; also Kirkwood et al., 1986). To get such values, it is
essential with proofreading processes. It can be estimated that this would correspond to a
loss of correct substrates through the proofreading step, that is the quantity above called
1, is about 20–30%, which is not a negligible energy or time loss in this process which
maybe is one of the most common, if not the most common, processes in a cell.
A pair of amino acids that have been particularly investigated because of a difficult
selection are isoleucine and valine. Both these have branched hydrocarbon side chains (see
Chapter 12), and that of isoleucine contains one methyl group (CH 3 ) more than valine. It is
a general fact that if a molecule with a large hydrocarbon group can be bound favourable to
an enzyme, then a slightly shorter chain can also be bound. This can be done by a pocket
into which the large group fits well. Then, also the short group fits. These amino acids also
have similar codes, and differ by the first base as isoleucine codes start with adenine while
valine codes start with guanine. There are reasonable ideas about the evolution of the genetic
code which propose that similar codes are results from the fact that these amino acids are
synthesised by similar processes. It is also reasonable that valine might be an early used
amino acid (it is the simplest of the two), while isoleucine is a later addition, produced by
an extension of valine production. The discrimination between isoleucine and valine is further
complicated as valine is more common and occurs more commonly in proteins than
isoleucine. Such non-mutual features should pose a problem for selection, and this might
be adjusted for by an appropriate choice of concentration ratios and, maybe, also modification
of the selection process features. As for isoleucine and valine, it was suggested that the
proofreading (rejection) step goes over a state where a wrong substrate, that is valine, is best
bounded and then the rejection rate gets a further factor larger than that of isoleucine. This
requires that a major competitor is recognised and then can be selected against.
30F
Further features of selection: error propagation
There are a number of quite interesting features associated with the selection processes. At
an early stage, one found and could study variations of protein accuracy in bacteria. One
got information from mutant bacteria where the accuracy could change; in particular, it
could increase. Then, one can influence the selection process by the antibiotics streptomycin,
which becomes attached at the ribosomes and then influences the selection of tRNA
and amino acid insertion at proper places of proteins.
The fact that normal bacteria keeps a particular selection accuracy, and that there are
mutants, which should be regarded as “less fitted”, seems to indicate that the “normal”
accuracy level is chosen according to some criteria as advantageous, such as optimising
some “cost” or time for producing functioning components, what was suggested above. As
should be expected according to the general principles, a higher accuracy also requires a
prolonged process time.
Streptomycin makes the selection worse, leading to a decrease of accuracy (Gorini,
1974; Rosenberger, 1982; Ruusala and Kurland, 1984.). There has sometimes been a misunderstanding
that the general theory would mean that this would imply a shorter process
time. However, a close look at the formalism above, how various rates influence the accuracy,
and what an optimised situation should look like, would show that there are no clear
relations between time and accuracy in a deteriorated, non-optimised selection process.