bird, or hunting instincts into the brain of a dog? In short, how is it that
merely by dictating which proteins are to be produced in cells, DNA exer-
cises such spectacularly precise control over the exact structure and func-
tion of macroscopic living objects? There are two major distinct problems
here. One is that of cellular differentiation: how do different cells, sharing
exactly the same DNA, perform different roles-such as a kidney cell, a
bone marrow cell, and a brain cell? The other is that of morphogenesis ("birth
of form"): how does intercellular communication on a local level give rise to
large-scale, global structures and organizations-such as the various organs
of the body, the shape of the face, the suborgans of the brain, and so on?
Although both cellular differentiation and morphogenesis are poorly un-
derstood at present, the trick appears to reside in exquisitely fine-tuned
feedback and "feedforward" mechanisms within cells and between cells,
which tell a cell when to "turn on" and when to "turn off" production of
various proteins.
Feedback and FeedforwardFeedback takes place when there is too much or too little of some desired
substance in the cell; then the cell must somehow regulate the production
line which is assembling that substance. Feedforward also involves the
regulation of an assembly line, but not according to the amount of end
product present; rather, according to the amount of some precursor of the
end product of that assembly line. There are two major devices for achiev~
ing negative feedforward or feedback. One way is to prevent the relevant
enzymes from being able to perform--that is, to "clog up" their active sites.
This is called inhibition. The other way is to prevent the relevant enzymes
from ever being manufactured! This is called repression. Conceptually,
inhibition is simple: you just block up the active site of the first enzyme in
the assembly line, and the whole process of synthesis gets stopped dead.Repressors and InducersRepression is trickier. How does a cell stop a gene from being expressed?
The answer is, it prevents it from ever getting transcribed. This means that
it has to prevent RNA polymerase from doing its job. This can be ac-
complisheQ by placing a huge obstacle in its path, along the DNA, precisely
in front of that gene which the cell wants not to get transcribed. Such
obstacles do exist, and are called repressors. They are themselves proteins,
and they bind to special obstacle-holding sites on the DNA, called (I am not
sure why) operators. An operator therefore is a site of control for the gene
(or genes) which immediately follow it; those genes are called its operon.
Because a series of enzymes often act in concert in carrying out a long
chemical transformation, they are often coded for in sequence; and this is
why operons often contain several genes, rather than just one. The effect
of the successful repression of an operon is that a whole series of genes is(^544) Self-Ref and Self-Rep