A Critique of Pure (Genetic) Information

138 Chapter 4
A DNA probe must satisfy two requirements. It must have the correct
sequence to bind to the gene of interest (and no unrelated genes) through
complementary base pairing with the target DNA (that has been uncoupled
from its double helix complement by being separated into single
strands). And it must also be linked to some visualizable marker in order
to enable the investigator to locate it. When a DNA probe derived from
one species is successful at locating a target sequence in another species,
it suggests that the target sequence has been highly conserved over evolutionary
time and is thus likely to be of much biological significance. In
the absence of a need for preserving the specific sequence, it is expected
that the identity of DNA bases will mutate at a regular rate.
Localization by complementary binding studies, using a src probe
derived from chicken to scan the DNA of a variety of other avian species
including the Australian emu, indicated that the src gene was highly conserved
in avian phylogeny and thus likely to be of functional significance
for the host. The level of interspecies sequence variation, as assessed by
molecular hybridization studies, was consistent with the characterization
of src as a highly conserved gene (Varmus 1989). In order to gain further
confirmation of the nonviral origins of homologous src genes, full
sequence analysis would have to be performed (i.e., the gene would have
to be cloned and sequenced). The homologous genes found in the
genomes of other avian species were referred to as “c-src,” for cellular
src. Sequence analysis of c-src demonstrated the presence of introns (noncoding
intervening sequences), where “endogenous virogenes have the
insignia of provirus, being composed of continuous coding domains,
flanked by repeated sequences” (Varmus 1989). Introns are the intervening
sequences of DNA which are found in eukaryotic genomes but
not prokaryotic or viral genomes. Their presence in c-src genes again
suggested that c-src was not of viral origin. Identification of the source
of the viral src oncogene as a putatively functional host gene led the
research program in molecular oncology back to the framework of a
somatic mutation model.
We said that the RSV transforming gene is indeed represented in normal cellular
DNA, but not in the form proposed by the virogene-oncogene hypothesis.
Instead, we argued, the cellular homolog is a normal cellular gene, which is introduced
into a retroviral genome in slightly altered form during the genesis of RSV.