trans

26 PARASITE GENOMICS
rapid and divergent evolution in the recent
(geological) past, and that the human parasites
arose from parasites of domesticated animals.
Genome-based research on other platyhelminths
is in its infancy, with only a small
number of ESTs from Echinococcus spp. available
(Table 1.2). Most if not all platyhelminths
use a 5 trans-spliced leader sequence, which
differs between species, to cap some of their
mRNAs, and platyhelminths may also utilize
an operonic gene organization.
Parasite vector genomes
The sequence of the host genome (human) for
the major human parasites is available in draft,
allowing parasitologists to investigate possible
interactions between parasite and host. Many
parasites also pass through intermediate or
vector hosts, and thus the genomes of these
vector species are also being investigated. For
some arthropod vectors, additional urgency is
afforded by their being vectors also for viral
and protozoal diseases. The mosquitoes Aedes
aegypti and Anopheles gambiae have genomes
significantly larger than that of the model
dipteran, D. melanogaster, but much of this
increase in genome size appears to be due to a
higher proportional content of repetitive and
retrotransposon DNA. Genetic maps are well
advanced for mosquitoes, particularly A. gambiae,
and loci conferring relative resistance
to vectoring filarial nematodes have been
mapped. Genomic sequencing has been initiated
based on physical maps spanning these
and other important vector traits. Similarly, the
Schistosoma mansoni snail host, Biomphalaria
glabrata, has been analysed using EST techniques
to investigate the schistosome–snail
interaction, and the basis of differential vectoring
capacity in snail populations. Analysis of
the B. glabrata genome is hampered by the lack
of genomics data from any closely related
comparators. The tick vector for Babesia,
Boophilus microplus, has been the subject of a
small EST project aimed at discovery of protein
products involved in feeding, for vaccine
development (see Table 1.2).
Genomics analyses have yet to be applied to
other metazoan parasites in any major way.
Small sequence datasets are available for the
medicinal leech Hirudo medicinalis, and for
scab and scabies mites (Psoroptes ovis and
Sarcoptes scabei) (see Table 1.2).
THE FUTURE
The past ten years have seen the emergence of
genomics as a field, and the application of
genomics analyses to problems of parasite biology.
The future of this mode of analysis is
bright. As genome datasets reach completion
(for example, the P. falciparum genome is ‘essentially
finished’ and other protozoa are not
far behind) the opportunities for whole-system
analyses will grow. What metabolic pathways
are present in the chosen parasite? Which are
absent? Do these metabolic data suggest essential
bottleneck enzymes that might be good
drug targets? What potential immunomodulators
does the parasite genome encode, and how
might these function in the context of the host
or vector genome? Can the evolutionary history
of the origins of parasitism be read from comparison
between free-living and parasitic
species? Does this information suggest potential
routes to effective intervention? Which
genes are behaving anomalously compared to
their genomic environment? Are these possible
virulence factors, evolving rapidly in a Red
Queen race with host defences? Can the genes
involved in susceptibility and resistance to
drugs be identified by a combination of genetics
and map-based cloning, or genome and
cDNA microarray screening? When a parasite is
MOLECULAR BIOLOGY