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8/9/2019 Origin of Viral Oncogenes
http://slidepdf.com/reader/full/origin-of-viral-oncogenes 1/2
Origin of viral Oncogenes
Regardless of how oncogenes induce cancers, it how seems
clear that retroviral oncogenes have evolved from normal cellular
protooncogenes. originally, it was thought that the cellular homologs of viral oncogenes might be relics of integrated retroviral proviruses.
However, this is clearly not the case. Comparisons of the nucleotide
sequences of viral oncogenes and the homologous cellular
protooncogenes have shown that these genes share major regions of
the sequence identity. The ey di!erence is that the celluar
protooncogenes contain intron, whereas viral oncogenes are single
e"ons. This is not consistent with the idea that cellular protooncogenes
have evolved from v#oncogenes on integrated proviruses. $nstead, it
strongly suggest that v#oncogenes are derived from ancestral cellular
protooncogenes. This di!erence is to be e"pected if the v#oncogenesevolved from cellular protooncogenes the retroviral genomes are R%&
and the intron sequences of R%& transcripts of protooncogenes should
be splice out during R%& processing. &ll the needs to occur is for an
mR%& copy of a protooncogene to be ligated into the R%& genome of a
retrovirus by a recombination mechanism that preserves the 'TR
regions of the viral genome. The viral reverse transcriptase will then
convert the mR%&#viral R%& hybrid into homologous (%& for
intregation into the host genome.
$n some case, di!erent retroviruses that infect distantly related
species have acquired copies of the same cellular protooncogene. $n
other case, closely related viruses contain oncogenes derived from
completely unrelated cellular protooncogenes.
)y comparing the nucleotide sequences of the v#oncogenes and
the homologous c#protooncogenes, the sites of the of breaage and
joining in the recombination events that gave rise to the v#oncogenes
can sometimes be identi*ed. $n other cases, e"tensive rearrangements
have occurred, maing it impossible to identify the sites or
recombination involved in the acquisition of the oncogenes by the
retrovirus. $n several cases, the viral oncogenes encode fusion proteinscontaining part of the gag protein and the oncogenes product. $n most
cases, the retroviral acquisition of an oncogene has been accompanied
by the loss of viral genetic material required for replication. +uch
defective viruses can integrate normally as proviruses, but can only
produce progeny viruses in the presence of a helper virus- that
provides the missing function .
C&%CR &+ TH %( /RO(0CT O1 & 20'T$+T/ /ROC++
8/9/2019 Origin of Viral Oncogenes
http://slidepdf.com/reader/full/origin-of-viral-oncogenes 2/2
1inally, we should emphasi3e that a large amount of data
indicates that the cancerous state is the end product of a multistep
process. The cell lines used in transfection e"periment are probably
already at some intermediate stage in the pathway, possibly simply
due to the selection for the ability to grow under cell calture conditions. The oncogenes#induced transformation observed in cell cultures is
undoubtedly only one part of a more comple" pathway.
$n fact, there is considerable evidence indicating that certain
oncogenes may have cooperative e!ect in promoting neoplastic
transformation. 2oreover, di!erent oncogenes seem to play di!erent
roles in oncogenic pathways in di!erent cell types. 1inally, seems liely
that di!erent molecular events are involved in the acquisition of the
enhanced proliferative capacity of cells, in the ability of tumors to
invade adjacent tissues, and in the capacity for metastasis. To whate"tent and in what roles protooncogenes and oncogenes are involve in
these processes in human cancers remain to be determined.
Regardless of the e"tent of their involvement in the formation of
malignant tumors, the ongoing and future investigation of
protooncogenes and oncogenes promise to yield important information
about the molecular circuitry that controls cell proliferation in higher
eucaryotes such as humans.
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