Rare genotype advantage WORLD OF MICROBIOLOGY AND IMMUNOLOGY480•
turnover of the particular protein. In another experimental
approach, the protein constituents of bacteria or virusescan be
separated on an electrophoretic gel. The gel is then brought
into contact with X-ray film. Wherever a radioactive protein
band is present in the gel, the overlaying film will be exposed.
Thus, the proteins that are radioactive can be determined.
The use of radiolabeled compounds that can be utilized
as nutrients by bacteria allows various metabolic pathways to
be determined. For example, glucose can be radiolabeled and
its fate followed by various techniques, including chromatog-
raphy, autoradiography, and gel electrophoresis. Furthermore,
a molecule such as glucose can be radiolabeled at various
chemical groups within the molecule. This allows an investi-
gator to assess whether different regions of a molecule are
used preferentially.
Radiolabeling has allowed for great advances in micro-
biological research. A well-known example is the 1952 exper-
iment by Hershey and Chase, which established that DNA was
the reservoir of genetic information. Bacterial viruses were
exposed to either radioactive sulfur or phosphorus. The sulfur
radiolabeled the surface of the virus, while the phosphorus
labeled the DNA. Viruses were allowed to infect bacteria and
then were mechanically sheared off of the bacteria. The
sheared viruses were then collected separately from the bacte-
ria. Radioactive sulfur was found in the virus suspension and
radioactive phosphorus was found in the bacteria.
Furthermore, the bacteria eventually produced new virus,
some of which had radioactive DNA. Thus, radiolabeling
demonstrated the relationship between DNA and genetic
information.See alsoLaboratory methods in microbiologyRRare genotype advantageARE GENOTYPE ADVANTAGE
Rare genotypeadvantage is the evolutionary theory that geno-
types (e.g., the genes of a bacterium or parasite) that have been
rare in the recent past should have particular advantages over
common genotypes under certain conditions.
Rare genotype advantage can be best illustrated by a
host-parasite interaction. Successful parasitesare those carry-
ing genotypes that allow them to infect the most common host
genotype in a population. Thus, hosts with rare genotypes,
those that do not allow for infection by the pathogen, have an
advantage because they are less likely to become infected by
the common-host pathogen genotypes. This advantage is tran-
sient, as the numbers of this genotype will increase along with
the numbers of pathogens that infect this formerly rare host.
The pattern then repeats. This idea is tightly linked to the so-
called Red Queen Hypothesis first suggested in 1982 by evo-
lutionary biologist Graham Bell (1949– ) (so named after the
Red Queen’s famous remark to Alice in Lewis Carroll’s
Through the Looking Glass:“Now here, you see, you have to
run as fast as you can to stay in the same place.”). In other
words, genetic variation represents an opportunity for hosts to
produce offspring to which pathogens are not adapted. Then,
sex, mutation, and genetic recombinationprovide a movingtarget for the evolutionof virulence by pathogens. Thus, hosts
continually change to stay one step ahead of their pathogens,
likened to the Red Queen’s quote.
This reasoning also works in favor of pathogens. An
example can be derived from the use of antibioticson bacter-
ial populations. Bacterial genomes harbor genes conferring
resistance to particular antibiotics. Bacterial populations tend
to maintain a high level of variation of these genes, even when
they seem to offer no particular advantage. The variation
becomes critical, however, when the bacteriaare first exposed
to an antibiotic. Under those conditions, the high amount of
variation increases the likelihood that there will be one rare
genotype that will confer resistance to the new antibiotic. That
genotype then offers a great advantage to those individuals. As
a result, the bacteria with the rare genotype will survive and
reproduce, and their genotype will become more common in
future generations. Thus, the rare genotype had an advantage
over the most common bacterial genotype, which was suscep-
tible to the drug.See alsoAntibiotic resistance, tests for; Evolution and evolu-
tionary mechanisms; Evolutionary origin of bacteria and
virusesRRecombinant DNA moleculesECOMBINANTDNA MOLECULES
Recombinant deoxyribonucleic acid(DNA) is genetic material
from different organisms that has been chemically bonded
together to form a single macromolecule. The recombination
can involve the DNA from two eukaryotic organisms, two
prokaryotic organisms, or between an eukaryote and a
prokaryote. An example of the latter is the production of
human insulin by the bacterium Escherichia coli,which has
been achieved by splicing the genefor insulin into the E. coli
genome such that the insulin gene is expressed and the protein
product formed.
The splicing of DNA from one genome to another is
done using two classes of enzymes. Isolation of the target
DNA sequence is done using restriction enzymes. There are
well over a hundred restriction enzymes, each cutting in a very
precise way a specific base of the DNA molecule. Used singly
or in combination, the enzymes allow target segments of DNA
to be isolated. Insertion of the isolated DNA into the recipient
genome is done using an enzyme called DNA ligase.
Typically, the recombinant DNA forms part of the DNA
making up a plasmid. The mobility of the plasmid facilitates
the easy transfer of the recombinant DNA from the host organ-
ism to the recipient organism.
Paul Bergof Stanford University first achieved the man-
ufacture of recombinant DNA in 1972. Berg isolated a gene
from a human cancer-causing monkey virus, and then ligated
the oncogeneinto the genome of the bacterial virus lambda.
For this and subsequent recombinant DNA studies (which fol-
lowed a voluntary one-year moratorium from his research
while safety issues were addressed) he was awarded the 1980
Nobel Prize in chemistry.womi_R 5/7/03 8:17 AM Page 480