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information and the energy to execute such information can be defined as a machine
(Ji 1991), and since structural genes possess (1) genetic information encoded in their
nucleotide sequences and (2) mechanical energy stored in their conformational strains,
structural genes satisfy the necessary and sufficient condition for being molecular
machines . Extending this argument further, it is here suggested that:
Not only structural genes but also any DNA segment or the DNA molecule itself can be
viewed as molecular machines since they all participate in controlling one or more
phenotypes. (12.23)
Statement 12.23 will be referred to as the “Genes as Molecular Machines
Postulate” (GAMMP).
One indirect evidence for the GAMM Postulate is provided by the energy-
dependency of the self-regulatory powers of structural genes that can be estimated
from the GSvPD plots such as shown in Fig. 12.21 . As summarized in Table 12.8 ,
the slopes of the GSvPD plots of most metabolic pathways decrease (except for
the heme biosynthesis and oxphos pathways) as the budding yeast cell undergoes
cell-state transition from the energy-poor early to the energy-rich late phases. The
corresponding self-regulatory powers of structural genes increase by 53-162%
(see the last column in Table 12.8 ), indicating that the regulatory activity of
structural genes are generally enhanced by the availability of metabolic energy.
A structural gene can regulate its transcript level inside the cell as summarized
in Table 12.8 .
Mechanisms A, C, E , and G are trans-mechanisms, i.e., genes exert their control
power through other molecules such as RNA, whereas Mechanisms B, D, F, and
H represent both trans- and cis-mechanisms , the cis -mechanisms implicating genes
regulating other genes directly (e.g., via transmitting mechanical or conformational
strains), without being mediated by other molecules such as RNAs or proteins. The
cis -regulatory mechanisms of structural genes postulated here appear to be new but
are consistent with the ideas already discussed earlier - (1) the Bianchini cone in
Fig. 9.2 which represents the set of the mechanisms by which DNA itself regulate
transcription without being mediated by RNA or proteins, and (2) the concept of
d-genes (see Fig. 11.8 ), i.e., the notion that the DNA molecule as a whole acts as a
gene, for example, in self-replication where DNA acts as its own template.
One way to characterize the mechanism underlying the self-regulatory power
of a structural gene is to represent it as a vector in an eight-dimensional
“mechanisms space” defined by eight orthogonal axes, each encoding the extent
(with numerical values ranging from 0 to 1) of the contribution of one of the eight
mechanisms, A through H, shown in Table 12.9 , to the overall mechanism of
self-regulation, M i :
! ¼
M i
M i ð
c i1 ;
c i2 ;
c i3 ; :::;
c i8 Þ
(12.24)
where the subscript, i, refers to the ith RNA under consideration, and c i1 ,c i2 ,ci 3 ,
...
! , whose base is located at
the origin of the eight-dimensional mechanisms space.
,c i8 are the coordinates of the head of the vector , M i
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