Biology Reference
In-Depth Information
examined. Of the entire
A. suum
gene set, 2370 genes (representing 279
known biological pathways) had an orthologue in the KEGG database,
with close agreement (95%) to the representation of such orthologues in
C. elegans
, suggesting that the gene set is complete. Using homology data
for model organisms, including
C. elegans
,
Drosophila melanogaster
,
Saccharomyces cerivisiae
, and
Mus musculus
, and information available in
all accessible protein and/or conserved protein domain databases, we
were able to assign possible functions to
70% of the genes predicted for
>
A. suum
.
Molecular Groups Involved in Key Biological Functions
Transporters and Channels
Receptors and transporters play central functional roles in the cell.
Examples of key groups among these proteins are G-Protein Coupled
Receptors (GPCRs), which interact with GTPases and are involved in
a large range of signal transduction pathways. A range of transport
proteins (i.e. channels, pores, and porters) are also important, which
enable the active or passive transport of molecules and/or ions across
phospholipid membranes. Based on homology to curated GPCR data-
bases (e.g. GPCR-SARFARI and IUPHAR, accessible via
www.ebi.ac.uk
and
www.iuphar-dg.org
, respectively), we predicted
280 GPCRs for
A. suum
, including 166 class A rhodopsin-like, 97 class B secretin-like,
9 class C metabotropic glutamate/pheromone family, and 6 frizzled
receptors. In addition, of
w
1800 transporters predicted to be encoded in
the
A. suum
genome,
11
we identified 477 channel or pore proteins,
including 272 voltage-gated (VICs) and 98 ligand-gated (LICs) ion chan-
nels. VICs are activated by the electro-potential gradient across cellular
membranes, play key roles in the cell, including the transmission of nerve
impulses and the excitation of muscle fibers, and thus represent potent
targets for new nematocides. LICs are activated through the specific
binding of a ligand (e.g. acetylcholine) and are known targets for nema-
tocidal drugs, such as macrocyclic lactones (e.g. ivermectin),
57
levami-
sole,
58
and aminoacetonitrile derivatives (AAD).
59
Given the history of
LICs as drug targets, these proteins remain a major resource for novel
anti-parasite compounds. In addition, we detected 462 transporters (e.g.
small molecule porter proteins), of which the major facilitators (
n
>
¼
155),
cation symporters (
n
¼
71), and resistance-nodulation-cell division (RND;
n
¼
56) superfamilies were most abundant. These proteins are usually
associated with the transport, via diffusion or pumping, of small mole-
cules and/or ions (e.g. potassium, hydrogen, glucose or sodium ions)
across cellular membranes. Porters are essential for maintaining os-
motic balance between the cell and the external milieu, generating
