Biology Reference
In-Depth Information
The most striking observation that emerged from the study of phage production by
lysogenic bacteria and of induction of -galactosidase synthesis was the extraordi-
nary degree of analogy between the two systems. Despite the obvious differences
between the production of a virus and that of an enzyme, the evidence showed
that in both cases protein synthesis is subject to a
double genetic determinism
:on
the one hand, by
structural genes
, which specify the configuration of the peptide
chains; on the other hand, by
regulatory genes
, which control the expression of
these structural genes. In both cases, the properties of mutants showed that the
effect of a regulatory gene consists in inhibiting the expression of the structural
genes, by forming a cytoplasmic product which was called the
repressor
. In both
cases, the induction of synthesis (whether of phage or of enzyme) seemed to result
from a similar process:
an inhibition of the inhibitor
.
(Jacob, 1966, p. 1472)
The model explains genetic regulation through feedback, which is doubtless
the reason Monod was inclined at one point to think of it as a cybernetic
system. The molecularly characterized feedback relations supposedly brought
cybernetic feedback within the scope of 'strong reduction'. We will describe
the development and motivation for the model through the mid-1960s. In this
context, that will be sufficient to see how it functions as a mechanistic model.
In another paper, we intend to pursue the later development of the model.
In rough outline, in 1961, Monod and Jacob claimed that the
lac
operon
consists of a regulatory region (the operator) and a set of structural genes (see
Fig. 4). The operator, as they described it, consists of a promoter region, and
a repressor. There are three structural genes regulated by the operator.
5
One of
these structural genes codes for a permease that facilitates the uptake of lac-
tose from the environment. One codes for -galactosidase, an enzyme that cuts
lactose (a dissacharide) into two simpler sugars, which can then be utilized in
metabolism. In the presence of nutrient sources other than lactose, both the per-
mease and the -galactosidase are present but in extremely low concentrations.
When lactose is present and other sugars are not, the concentrations of these
products can increase by as much as a 1000-fold.
The crucial phenomenon, leading to the discovery of the
lac
operon, was
the discovery of biphasic growth of
E. coli
bacteria in carbohydrate mixtures
in the early 1940s by Monod (see Fig. 5). These results were associated by
Andre Lwoff with what he called 'enzymatic adaptation'. In the late 1940s,
Monod saw that even in the presence of lactose in the medium, there is no
-galactosidase present if there are other sugars, which we now know means
there is no expression of the
lac
operon; that is, with glucose present, lactose
fails to induce the
lac
operon, and the organism does not metabolize lactose.
5
In their original work, Monod and Jacob recognized only two structural genes. That does not change the
substance of our discussion, but there are clearly three.
