KEY TERMS:
- The central dogma describes the basic nature of genetic information: sequences of nucleic acid can be perpetuated and interconverted by replication, transcription, and reverse transcription, but translation from nucleic acid to protein is unidirectional, because nucleic acid sequences cannot be retrieved from protein sequences.
- A retrovirus is an RNA virus with the ability to convert its sequence into DNA by reverse transcription.
- Reverse transcription is synthesis of DNA on a template of RNA. It is accomplished by the enzyme reverse transcriptase.
- Cellular genes are DNA, but viruses and viroids may have genes of RNA.
- DNA is converted into RNA by transcription, and RNA may be converted into DNA by reverse transcription.
- The translation of RNA into protein is unidirectional.
The central dogma defines the
paradigm of molecular biology. Genes are perpetuated as sequences of nucleic
acid, but function by being expressed in the form of proteins. Replication is
responsible for the inheritance of genetic information. Transcription and
translation are responsible for its conversion from one form to another.
Figure 1.43 illustrates the roles of
replication, transcription, and translation, viewed from the perspective of the
central dogma:
- The perpetuation of nucleic acid may involve either DNA or RNA as the genetic material. Cells use only DNA. Some viruses use RNA, and replication of viral RNA occurs in the infected cell.
- The expression of cellular genetic information usually is unidirectional. Transcription of DNA generates RNA molecules that can be used further only to generate protein sequences; generally they cannot be retrieved for use as genetic information. Translation of RNA into protein is always irreversible.
These mechanisms are equally effective for the cellular
genetic information of prokaryotes or eukaryotes, and for the information
carried by viruses. The genomes of all living organisms consist of duplex DNA.
Viruses have genomes that consist of DNA or RNA; and there are examples of each
type that are double-stranded (ds) or single-stranded (ss). Details of the
mechanism used to replicate the nucleic acid vary among the viral systems, but
the principle of replication via synthesis of complementary strands remains the
same, as illustrated in Figure 1.44.
Cellular genomes reproduce DNA by the mechanism of
semi-conservative replication. Double-stranded virus genomes, whether DNA or
RNA, also replicate by using the individual strands of the duplex as templates
to synthesize partner strands.
Viruses with single-stranded genomes use the single strand
as template to synthesize a complementary strand; and this complementary strand
in turn is used to synthesize its complement, which is, of course, identical
with the original starting strand. Replication may involve the formation of
stable double-stranded intermediates or use double-stranded nucleic acid only as
a transient stage.
The restriction to unidirectional transfer from DNA to RNA
is not absolute. It is overcome by the retroviruses, whose genomes consist of single-stranded
RNA molecules. During the infective cycle, the RNA is converted by the process
of reverse transcription into a single-stranded
DNA, which in turn is converted into a double-stranded DNA. This duplex DNA
becomes part of the genome of the cell, and is inherited like any other gene.
So reverse transcription allows a sequence of RNA to be retrieved and used
as genetic information.
The existence of RNA replication and reverse transcription
establishes the general principle that information in the form of either
type of nucleic acid sequence can be converted into the other type. In the
usual course of events, however, the cell relies on the processes of DNA
replication, transcription, and translation. But on rare occasions (possibly
mediated by an RNA virus), information from a cellular RNA is converted into DNA
and inserted into the genome. Although reverse transcription plays no role in
the regular operations of the cell, it becomes a mechanism of potential
importance when we consider the evolution of the genome.
The same principles are followed to perpetuate genetic
information from the massive genomes of plants or amphibians to the tiny genomes
of mycoplasma and the yet smaller genetic information of DNA or RNA viruses. Figure 1.45 summarizes some examples that illustrate the
range of genome types and sizes.
Throughout the range of organisms, with genomes varying in
total content over a 100,000 fold range, a common principle prevails. The
DNA codes for all the proteins that the cell(s) of the organism must synthesize;
and the proteins in turn (directly or indirectly) provide the functions needed
for survival. A similar principle describes the function of the genetic
information of viruses, whether DNA or RNA. The nucleic acid codes for the
protein(s) needed to package the genome and also for any functions additional to
those provided by the host cell that are needed to reproduce the virus during
its infective cycle. (The smallest virus, the satellite tobacco necrosis
virus [STNV], cannot replicate independently, but requires the simultaneous
presence of a "helper" virus [tobacco necrosis virus, TNV], which is itself a
normally infectious virus.)
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