Veterinary Science Collected Works - Research Publications
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ItemIdentification, distribution and molecular evolution of the pacifastin gene family in Metazoa.(Springer Science and Business Media LLC, 2009-05-12)BACKGROUND: Members of the pacifastin family are serine peptidase inhibitors, most of which are produced as multi domain precursor proteins. Structural and biochemical characteristics of insect pacifastin-like peptides have been studied intensively, but only one inhibitor has been functionally characterised. Recent sequencing projects of metazoan genomes have created an unprecedented opportunity to explore the distribution, evolution and functional diversification of pacifastin genes in the animal kingdom. RESULTS: A large scale in silico data mining search led to the identification of 83 pacifastin members with 284 inhibitor domains, distributed over 55 species from three metazoan phyla. In contrast to previous assumptions, members of this family were also found in other phyla than Arthropoda, including the sister phylum Onychophora and the 'primitive', non-bilaterian Placozoa. In Arthropoda, pacifastin members were found to be distributed among insect families of nearly all insect orders and for the first time also among crustacean species other than crayfish and the Chinese mitten crab. Contrary to precursors from Crustacea, the majority of insect pacifastin members contain dibasic cleavage sites, indicative for posttranslational processing into numerous inhibitor peptides. Whereas some insect species have lost the pacifastin gene, others were found to have several (often clustered) paralogous genes. Amino acids corresponding to the reactive site or involved in the folding of the inhibitor domain were analysed as a basis for the biochemical properties. CONCLUSION: The absence of the pacifastin gene in some insect genomes and the extensive gene expansion in other insects are indicative for the rapid (adaptive) evolution of this gene family. In addition, differential processing mechanisms and a high variability in the reactive site residues and the inner core interactions contribute to a broad functional diversification of inhibitor peptides, indicating wide ranging roles in different physiological processes. Based on the observation of a pacifastin gene in Placozoa, it can be hypothesized that the ancestral pacifastin gene has occurred before the divergence of bilaterian animals. However, considering differences in gene structure between the placozoan and other pacifastin genes and the existence of a 'pacifastin gene gap' between Placozoa and Onychophora/Arthropoda, it cannot be excluded that the pacifastin signature originated twice by convergent evolution.
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ItemNo Preview AvailableA Genome Wide Survey of SNP Variation Reveals the Genetic Structure of Sheep Breeds(PUBLIC LIBRARY SCIENCE, 2009-03-03)The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through genome-wide association studies, genomic selection and the dissection of quantitative traits. After identifying the first genome-wide set of SNP for sheep, we report on levels of genetic variability both within and between a diverse sample of ovine populations. Then, using cluster analysis and the partitioning of genetic variation, we demonstrate sheep are characterised by weak phylogeographic structure, overlapping genetic similarity and generally low differentiation which is consistent with their short evolutionary history. The degree of population substructure was, however, sufficient to cluster individuals based on geographic origin and known breed history. Specifically, African and Asian populations clustered separately from breeds of European origin sampled from Australia, New Zealand, Europe and North America. Furthermore, we demonstrate the presence of stratification within some, but not all, ovine breeds. The results emphasize that careful documentation of genetic structure will be an essential prerequisite when mapping the genetic basis of complex traits. Furthermore, the identification of a subset of SNP able to assign individuals into broad groupings demonstrates even a small panel of markers may be suitable for applications such as traceability.
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ItemIn Vivo Yeast Cell Morphogenesis Is Regulated by a p21-Activated Kinase in the Human Pathogen Penicillium marneffei(PUBLIC LIBRARY SCIENCE, 2009-11)Pathogens have developed diverse strategies to infect their hosts and evade the host defense systems. Many pathogens reside within host phagocytic cells, thus evading much of the host immune system. For dimorphic fungal pathogens which grow in a multicellular hyphal form, a central attribute which facilitates growth inside host cells without rapid killing is the capacity to switch from the hyphal growth form to a unicellular yeast form. Blocking this transition abolishes or severely reduces pathogenicity. Host body temperature (37 degrees C) is the most common inducer of the hyphal to yeast transition in vitro for many dimorphic fungi, and it is often assumed that this is the inducer in vivo. This work describes the identification and analysis of a new pathway involved in sensing the environment inside a host cell by a dimorphic fungal pathogen, Penicillium marneffei. The pakB gene, encoding a p21-activated kinase, defines this pathway and operates independently of known effectors in P. marneffei. Expression of pakB is upregulated in P. marneffei yeast cells isolated from macrophages but absent from in vitro cultured yeast cells produced at 37 degrees C. Deletion of pakB leads to a failure to produce yeast cells inside macrophages but no effect in vitro at 37 degrees C. Loss of pakB also leads to the inappropriate production of yeast cells at 25 degrees C in vitro, and the mechanism underlying this requires the activity of the central regulator of asexual development. The data shows that this new pathway is central to eliciting the appropriate morphogenetic response by the pathogen to the host environment independently of the common temperature signal, thus clearly separating the temperature- and intracellular-dependent signaling systems.
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ItemDharma as Man : A Myth of Jesus in Buddhist Lands(Uni-Verity Press, 2009)A rendering of the combined Christian gospels into Buddhist concepts and language in a setting consistent with the India of today and 200 years ago.