Biology Reference
In-Depth Information
Nemazee, 2000) and it is difficult to see how it could be compati-
ble with the deterministic model. The latter indeed predicts that
genes in the same microenvironment, and therefore influenced by
the same transcriptional regulatory factors, should be in the same
state of activity or inactivity. Yet this is not the case for all these
genes. Their alleles are located in the same nucleus but they are not
expressed in the same way on the two chromosomes that carry
them. The simplest interpretation to explain this is that gene
expression is a stochastic phenomenon. An allele is expressed on one
chromosome but not necessarily on the other at the same time, for
each allele only has a certain probability of being expressed at a
given moment. This explanation has been confirmed by experi-
ments, in which in the bacterium
Escherichia coli
and the yeast
Saccharomyces cerevisae
, two copies of a single gene, artificially
placed in strictly identical intracellular contexts, are not tran-
scribed in the same way at a given moment. Their expression
undergoes major stochastic fluctuations (Elowitz
et al
., 2002; Raser
and O'Shea, 2004).
All these data suggest a probabilistic interpretation, advanced
by most of the authors. Activation of gene transcription would seem
to be limited by assembly of the protein complex which initiates it.
Very many different molecules participate in forming this complex
but there are very few of some of these proteins in the cell nucleus.
As they have to diffuse right to the transcription initiation site to
assemble, this is a rare occurrence and there is only a small proba-
bility of it occurring at any given moment. When it does occur,
after the gene has been transcribed and the complex has dissoci-
ated, it is repeated after a period which varies randomly from one
time to the next (McAdams and Arkin, 1999; Hume, 2000; Paldi,
2003; Coulon
et al
., in press). A considerable amount of work has
been done to analyse this phenomenon precisely and quantitatively.
The result from it is that the stochastic expression of genes is nowa-
days considered an unquestionable fact (Kaern
et al
., 2005; Raser and
O'Shea, 2005; Kaufmann and van Oudenaarden, 2007; Heams, in
press). From a philosophical point of view, it can be interpreted objec-
tively (Merlin, in press).
