INTRONS AND EXONS
Once the genes of unrelated cells were studied it
became clear that the molecular genetics of higher
organisms are different from those of bacteria. The
principles uncovered in prokaryotes cannot simply be
applied to eukaryotes. For one thing, the precursor RNA
found in the nucleus, called heterogeneous nuclear RNA
(hnRNA), was far greater in amount than the mRNA that
emerged from the nucleus into the cytoplasm. It was
discovered that the linear hnRNA molecule contained
excess RNA which was cut out, and the mRNA was then
constructed from splicing together the in-between pieces.
An editing process had taken place.58 The logical inference
from this finding was that the genomic DNA from which
the hnRNA was transcribed must be similarly constructed.
The notion of the co-linear relationship between a segment
of DNA and the protein for which it codes is not true, at
least for higher organisms.
The word ‘intron’ was used to describe such a noncoding
region of a structural gene. They separate the
‘exons’, which encode the amino acids of the protein.59
For instance, the human b-globin gene comprises, in linear
sequence, three exons separated by two introns within a
total length of 1,600 nucleotides. Introns are abundant in
higher eukaryotes, uncommon in lower eukaryotes, and
rare in prokaryotic structural genes. Variations in the length
of the genes are primarily determined by the lengths of
the introns. Since the discovery of introns/exons the
intricate processes of nuclear mRNA splicing have been
elegantly elucidated. Among these are the remarkable selfsplicing
introns60 and the equally revolutionary finding that
individual nucleotides can be inserted into RNA after
transcription altering them remarkably.61
The inevitable questions emerged. What role does
having genes in pieces serve? How have such interrupted
genes ‘evolved’ over time?
One hypothesis points out that exons usually encode
for a part of the protein that folds to form a domain. What
constitutes a domain has been a matter of controversy. By
dispersing individual exons of a protein among introns it
is reasoned that breaking DNA and rejoining and
recombining different exons is that much easier. This
process of shuffling exons/domains is presumed to have
created new proteins with multi-domain structures. This
is thought to be a more efficient way for a cell to create
proteins rather than through random DNA mutations. Here
is a means of duplicating, modifying, assembling and
reassembling units with modular functions into larger
structures. According to this hypothesis this is the reason
why introns have survived through time. Several queries
may be raised. First, exon shuffling as a device to speed
up evolution is logically tied up with a subsidiary
assumption that possessing similar domains qualifies
proteins for biochemical kinship, which is to say, these
proteins are alleged to bear the marks of descent from a
common ancestral protein.62 But the construction of
phylogenetic trees relies on unstable molecular clocks and
other genetic mechanisms largely unknown63 and, as
discussed below, should be approached with caution.
Biochemical kinship aside, would not domains
exercising similar function be structurally alike such as
we see between, say, the catalytic domains of the two serine
proteases chymotrypsin and tissue plasminogen activator?
Second, RNA splicing is an accurate and complex
procedure comparable in complexity to protein synthesis
and initiation of transcription. It is carried out by a 50S to
60S ribonucleoprotein made up of small nuclear
ribonucleoproteins (snRNPs) as well as other proteins. Just
as the ribosome is built up in the process of translation,
the spliceosome components assemble in an orderly
manner on the intron to be spliced before the initial
cleavage of the 5' splice site. The splicing must be carried
out precisely, joining the 5' end of the preceding exon to
the 3' end of that following. A frameshift of even one
nucleotide would change the resulting mRNA message.
The inescapable conclusion is that these interlocking
components must have ‘evolved’ together, as an imperfect
splicing mechanism is worse than none.
Third, were the original protein-coding units seamless,
that is, uninterrupted by introns? And were the introns
bits of ‘selfish DNA’ that later insinuated themselves into
the hosts’ structural genes? What purpose then the
subsequent evolution of a multi-step complicated splicing
machinery to remove the introns?64-69 Would not simply
eliminating the introns make better sense for selective
advantage?
Fourth, and most importantly, transport of mRNA from
the nucleus to the cytoplasm is coupled to splicing and
does not occur until all the splicing is complete. How
does the RNA enter the cytoplasm for translation during
the evolution of the splicing mechanism? This would have
disrupted protein synthesis and would be powerfully
selected against.70-72 Why is splicing in all its variants so
rampant today?
The problem would arise too were introns abundant in
cells without nuclear membranes — the prokaryotes.
Mattick wrote:
‘If introns were introduced into a procaryotic cell’s
genes, there would be no opportunity to remove them
before protein is made, and the result would be
“nonsense” non-functional proteins.’73
This is essentially correct because spliceosomes would be
needed for their removal, but again begs the question on
the viability of the transitional phases.
The relationships between exons and protein domains
remain to be worked out. Where introns came from and
how they were integrated into the genome is a mystery to
evolutionists.74
