viruses may have many enzymes within the particle and hundreds of genes encoded by the nucleic acid.
Viral genomes are always very compact, with almost every nucleotide devoted to genes.
6.4.6. 1The Viral Life Cycle. First, a virus must enter its host cell. The simpler viruses then uncoat
completely and the DNA enters the nucleus where parts of its genome are transcribed. More complex
viruses, such as poxviruses preserve an internal core structure inside the cell, which stays in the cytoplasm.
In poxviruses, the host cell’s RNA polymerasecomponents migrate to the cytoplasm.
For most viruses, there is more than one stage of viral infection. For the simpler viruses there is an early
phase (pre-DNA replication) and a late phase (post-DNA replication). For DNA viruses the early phase
involves the transcription of ‘early’ genes, the jobs of which are to make sure the cell is not in a resting
phase and to coordinate the switching on of viral DNA replication and transcription of ‘late’ genes that
typically encode the components of the virus particle. For more complex viruses there are several phases,
for example herpesviruses have three distinct phases.
6.4.6.2 RNA Viruses. RNA viruses all encode their own polymerases for replication, because host
cells do not contain enzymes capable of copying RNA. () Strand viruses contain RNA that can act as an
mRNA for the production of the viral polymerase that is responsible for synthesis of a minus strand.
The/duplex (or replication intermediate) is then transcribed to generate further () strand, to thus
produce more mRNA as well as viral RNA. () Strand viruses cannot act as mRNA when they enter the
cell, so they must carry polymerase inside their virus particles. This polymerase then replicates the ()
strand, usually to form a/RNA duplex as before, which is then copied to produce mRNA.
One of the most interesting and important classes of RNA virus is the retroviruses.^30 These are () strand
viruses that depart from a normal life cycle by going through a DNA intermediate. The AIDS retroviruses
HIV 1 and 2 are major pathogens, which are responsible for the deaths of millions of people. Retroviruses
carry an RNA-dependent DNA polymerase (reverse transcriptase) that is responsible for the synthesis of
a double-stranded DNA copy of the viral RNA. This DNA copy is inserted into the chromosomal DNA by
another virus-encoded enzyme (integrase). The integrated DNA is then transcribed to produce () strand
RNA, which then can be processed to become mRNA or virus particle RNA.
An important feature of viruses is their high rate of sequence mutation. In some cases the consequences
are serious, since such mutation can lead to resistance to drug treatment or to antibodies raised by the
human immune system. Rapid sequence mutation in a virus is often due to the viral polymerase being
more error-prone than the cellular DNA polymerase. Since the viral life cycle is typically measured in
hours or a few days, a virus will go through many successive replications of its genome during an infec-
tion, each one of which can give rise to new mutations.
6.5 DNA Sequence and Bioinformatics
The remarkable advances in cloning and sequencing technologies since the 1970s have made it reasonably
easy to sequence very long stretches of DNA. Whole genome sequences are being deposited in sequence
databases at an accelerating rate.13,14The enormous amount of data involved in a genome sequence must be
stored in such databases and analysed. To get an idea of the volume of information, the complete sequence
of a single, smaller than average-sized human gene, the globin gene is shown (Figure 6.15). One thousand
such genes are represented below and 30 such sets are roughly equivalent to the complete human gene com-
plement. This constitutes about 1/60th of the entire human genome, with repetitious DNA making up the rest.
6.5.1 Finding Genes
The acquisition of complete genome sequences allows potential access to every gene in the organism. To
realise this goal, genes must be found within the ‘haystack’ of non-coding DNA. Bioinformaticsprovides
reasonably reliable search algorithms to predict gene structure, particularly for location of exonswithin
220 Chapter 6