Biology Reference
In-Depth Information
CONCLUSIONS, IMPLICATIONS, AND MAJOR
PROSPECTS FOR FUNDAMENTAL AND
APPLIED RESEARCH
Using massively parallel (Illumina) sequencing technology, we
sequenced the genome of A. suum from the reproductive tract of a single
adult female worm. 11 From six paired-end sequencing libraries (insert
sizes: 0.17 kb to 10 kb), we generated 39 Gb of usable short-read sequence
data, equating to
80-fold coverage (following filtering) of the 273 Mb
genome. We assembled the short-reads, constructed scaffolds, in a step-
by-step manner, and then closed intra-scaffold gaps. 16 Transposable
elements, non-coding RNAs, and the protein coding gene set were
inferred using a combined, predictive modeling and homology-based
approach. To enable gene predictions and explore key molecules associ-
ated with larval migration, reproduction, and development, we
sequenced messenger RNA from infective L3s (from eggs), migrating L3s
from the liver or lungs of the host, and L4s from the small intestine, as
well as muscle and reproductive tissues from adult male and female
worms. All proteins predicted from the gene set were annotated using
databases for conserved protein domains, GO annotations, and model
organisms (i.e. C. elegans , D. melanogaster , and M. musculus ). Essentiality
and drug target predictions were conducted using established methods.
The A. suum genome determined contains at least 18,500 protein-
coding genes, whose predicted products include
w
1800 channels and
transporters,
w
600 kinases,
>
600 receptors, and
w
450 peptidases.
Notably, the A. suum secretome (
750 molecules) is rich in peptidases,
which are likely linked to the penetration and degradation of host tissues,
and an assemblage of molecules likely to misdirect or weaken host
immune responses. This genome provides a comprehensive resource to
the scientific community for a range of future genomic, genetic, evolu-
tionary, biological, ecological, and epidemiological investigations and to
underpin the development of new interventions (drugs, vaccines and
diagnostic tests) against ascariasis and other helminthiases.
Although various studies have given improved insights into the
systematics, phylogeography, population genetics, biology, immunobiol-
ogy, and epidemiology of Ascaris using molecular tools 6 (see also
Chapters 1, 7, 8, and 10), there have been limited global studies of the
molecular biology, biochemistry, and physiology of Ascaris spp., para-
site
w
host relationships and ascariasis using -omic technologies. Charac-
terizing the genome and transcriptomes of A. suum using the advanced
technologies described here provides a solid foundation to explore the
systems biology of this parasite and design entirely new treatment,
diagnostic, and control strategies.
e
Search WWH ::




Custom Search