Biology Reference
In-Depth Information
If such polymorphism in Ascaris were found, how could it be investi-
gated at the genetic level? The sequencing of the A. suum genome
53
(see
Chapter 11) provides a base from which to search for polymorphisms in
the genomes of that species but also of A. lumbricoides. This can be done in
a number of ways using genetic material from samples from an outbred
population of the parasite. But a more directed approach might be to focus
on genes involved in surface and secreted materials using gene tran-
scription surveys that focus on mRNAs encoding polypeptides that
exhibit secretory signal peptides, although this might not include surface
antigens or carbohydrate epitopes. Genetic polymorphisms may appear
as differences in the sequences of proteins that would be under immune
selection (and the frequency of synonymous and non-synonymous
mutations), but also in the activity and specificity of enzymes involved
in the glycosylation of proteins and glycolipids, as is the case for the
evolution of human ABO blood groups.
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Apposite to this are the elegant
studies showing that surface antigens of C. elegans are diverse and under
the control of identifiable loci which, importantly, may encode glyco-
sylating enzymes.
55
e
57
Intriguingly, it was also shown that surface anti-
gens expressed by C. elegans can change under different culture
conditions.
58,59
This is a fascinating observation, and does mean that
parasitic species can also alter their antigens in response to the immune
responses they encounter in order to evade attack. The classic experi-
ments carried out in the 1970s on Nippostrongylus brasiliensis illustrated
that the secreted materials of a parasitic nematode can alter according to
whether or not a large infection is initiated at one time, or instead accu-
mulates as a trickle infection, or whether an immune response has been
mounted.
60
e
62
The possibility that parasitic nematodes may alter their
surface antigens and secretions in response to immunological and other
environmental cues is clearly one demanding detailed investigation.
Those original experiments with N. brasilieinsis concerned secreted
enzymes, but very little is known of the enzymes released by tissue-
invading Ascaris larvae, yet they could also be both diverse and their
release dependent on both innate and acquired immune responses by the
host. The proteinases released by infective and lung-stage larvae, and to
which neutralizing antibodies are produced, may be another good place
to start.
13
When one considers that the unequaled degree of polymorphism of
immunity-related genes in vertebrates is considered to be an evolutionary
response to a diverse range of pathogens that are themselves evolving to
circumvent immunity (discussed in ref.
63
) then there seems to be no
reason why a sexually reproducing parasite such as Ascaris will not itself
have evolved polymorphisms in order that its population will succeed in
polymorphic hosts. This would seem to be a simple prediction from the
Red Queen hypothesis.
64,65
An intriguing extra possibility would be that
