Control With
RNA
John Mattick has a very interesting article in the current
edition of Scientific American
(October 2004) entitled, The Hidden
Genetic Program of Complex Organisms. I plan to discuss his insights in more detail,
and how they relate to a teleological viewpoint, but for now I will just cite
some tantalizing excerpts. I do this
simply to offer free advertisement for his paper, as now is the time to pick up
this article at your local newsstand.
From Mattick:
Assumptions can be dangerous, especially in
science. They usually start as the most plausible or comfortable interpretation
of the available facts. But when their truth cannot be immediately tested and
their flaws are not obvious, assumptions often graduate to articles of faith,
and new observations are forced to fit them. Eventually, if the volume of
troublesome information becomes unsustainable, the orthodoxy must collapse. We
may be witnessing such a turning point in our understanding of genetic
information.
The
turning point Mattick speaks of concerns a very
crucial, functional role for RNA that extends further than scientists expected:
Proteins do play a role in the regulation of
eukaryotic gene expression, yet a hidden, parallel regulatory system consisting
of RNA that acts directly on DNA, RNAs and proteins
is also at work. This overlooked RNA-signaling network may be what allows
humans, for example, to achieve structural complexity far beyond anything seen
in the unicellular world.
Much of
this regulatory RNA is encoded among amidst the “junk DNA”, including what has
long been thought of as functionless introns:
But if introns
do not code for protein, then why are they ubiquitous among eukaryotes yet
absent in prokaryotes? Although introns constitute 95
percent or more of the average protein-coding gene in humans, most molecular
biologists have considered them to be evolutionary leftovers, or junk. Introns were rationalized as ancient remnants of a time
before cellular life evolved, when fragments of protein-coding information
crudely assembled into the first genes.
Mattick spells out the importance of this
RNA, acting as part of a parallel information processing system:
Put simply, the conundrum is this:
less than 1.5 percent of the human genome encodes proteins, but most of it is
transcribed into RNA. Either the human genome (and
that of other complex organisms) is replete with useless transcription, or
these nonprotein-coding RNAs
fulfill some unexpected function.
If this hypothesis is true, its
meaning may be profound. Eukaryotes (especially the more complex ones) may have
developed a genetic operating system and regulatory networks that are far more
sophisticated than those of prokaryotes: RNAs and
proteins could communicate regulatory information in parallel. Such an
arrangement would resemble the advanced information-processing systems
supporting network controls in computers and the brain.
Functional jobs in cells routinely
belong to proteins because they have great chemical and structural diversity.
Yet RNA has an advantage over proteins for transmitting information and
regulating activities involving the genome itself: RNAs
can encode short, sequence-specific signals as a kind of bit string or zip
code. These embedded codes can direct RNA molecules precisely to receptive
targets in other RNAs and DNA. The RNA and RNA-DNA
interactions could in turn create structures that recruit proteins to convert
the signals to actions. The bit string of addressing information in the RNA
gives this system the power of tremendous precision, just as the binary bit
strings used by digital computers do. It is not too much of a stretch to say
that this RNA regulatory system would be largely digital
in nature.
SUCH CONSIDERATIONS lead naturally to a more general consideration of what type of
information, and how much of it, might be required to program the development
of complex organisms. The creation of complex objects, whether houses or
horses, demands two kinds of specifications: one for the components and one for
the system that guides their assembly. (To build a house, one must specify the
needed bricks, boards and beams, but one must also have an architectural plan
to show how they fit together.) In
biology, unlike engineering, both types of information are encoded within one
program, the DNA. The component molecules that make up different organisms
(both at the individual and the species levels) are fundamentally alike: around
99 percent of the proteins in humans have recognizable equivalents in mice, and
vice versa; many of those proteins are also conserved in other animals, and
those involved in basic cellular processes are conserved in all in complex
networks essential to our biology. Thus, rather than the genomes of humans and
other complex organisms being viewed as oases of protein-coding sequences in a
desert of junk, they might better be seen as islands of protein-component information
in a sea of regulatory information, most of which is conveyed by RNA.
As I said, I’ll expand on all this at a later date. So run out and get your copy.