294 Raphael Falk
tion completely. It must be conceived as a generic, instrumental unit of function
at the molecular level of cellular (or, considering differentiation, even organismal)
system’s translation processes [Falk, 2000b]. Even the basic claim of the Cen-
tral Dogma that there cannot be any transfer of amino-acid sequence information
from one protein to another must be revised: obviously enzymatic processing of
pre-messenger RNA may significantly and specifically modify the message.
Yet, this did not relax the fixation on the reductionist molecular genetic analy-
sis, according to which all “information” for the development of organisms, their
growth and function is stored in the DNA and that this is the essence of life. The
impressive successes of genetic engineering, which allowed to strikingly manipulate
the phenotypes of organisms, only promoted the dogmatic notion of genetic deter-
minism. This was expressed most dramatically by Walter Gilbert, in support of
the effort to uncover the full DNA sequence of the genome, which he described as
“A vision of the holly Grail” [Gilbert, 1992]. When the Human Genome Project
idea started to gain momentum Gilbert presented a CD on which presumably the
full sequence of his DNA was stored, asserting: “This is me!”
As has been lately assessed by Mattick the effects of Crick’s Dogma will haunt
us still for may years to come:
The central dogma has... not only been taken to mean that most
genes encode proteins, but also that proteins are sufficient in them-
selves to specify and organize the autopoietic programming of complex
biological entities, an assumption that has pervaded molecular biology
for decades.... a second tier of genetic output and a network of parallel RNA-
mediated interactions has evolved in [complex] organisms, which may
enable the integration and coordination of sophisticated suites of gene
expression required for differentiation and development. [Mattick, 2003,
937]
It was only in recent years, after the intensive efforts of the complete sequencing
of the genomes of a large number of species, that the significance of the “non-
coding” sequences — sometimes even called “junk sequences” — and especially
their role through various kinds of regulatory RNAs (siRNA, miRNA, snoRNA,
snRNA, etc.) returned to center-stage (see, e.g., Chenet al.[2004]; Dennis [2002];
Enrightet al.[2003]; Moss and Poethig [2002]). Most of these RNAs act as short
segments that hybridize specifically to homologous RNA sequences. Some interfere
with translation reactions, others modify or split transfer-RNA or ribonsomal-
RNA molecules.
The failure to recognize the full implications of...the possibility that
the intervening noncoding sequences may be transmitting parallel in-
formation in the form of RNA molecules — may well go down as one of
the biggest mistakes in the history of molecular biology. (Gibbs [2003]
quoting Mattick)