In this thesis the evolution of the sghC1q gene family is explored throughout the metazoan lineage and within the zebrafish (Danio rerio) genome. This involved novel bioinformatic analyses, extensive synthesis of the literature, development of a bioinformatic tool, and the transcriptional assessment of the full complement of sghC1q genes within D. rerio during infection and early development.
The secreted globular head C1q (sghC1q) genes can be characterized as a family of genetic loci each encoding a signal peptide followed by a complement component 1q globular (gC1q) motif. Members of this family have been referred to as precerebellin-like (cblnl), C1q-like or ovary specific C1q-like factors. Previous studies have found gene family members in multiple organisms with varying numbers of copies within a species. The genes are known to be transcribed in response to infection and/or during development.
The domain of the C1q globular head (gC1q or ghC1q) appears to be ancient; present even in prokaryotes. With increasing complexity of organisms, this domain can sometimes be found accompanying first a signal peptide motif (indicative of secretion), and later with a collagen region. A comprehensive naming scheme is suggested based on these evolutionary adaptations. Computational modeling shows the globular head to be structurally conserved throughout the metazoa.
The EST Keeper program was developed to facilitate these studies in identification of sets of non-redundant homologous genes from BLAST results that often contain redundant copies and gene fragments. It was built as a Flash based webservice and can be used to find gene families within genomes and EST datasets.
Twenty sghC1q genes were found in the D. rerio genome (Zv9) and transcriptionally assessed. Two of the examined twenty genes showed significant up-regulation within 24 h of infection with the fish pathogen Streptococcus iniae, and eleven were expressed during early development. Due to the clustered nature of these genes on chromosomes two and seven, intrachromosomal duplication events are hypothesized and explored.
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|Advisor:||Gerwick, Lena G.|
|Commitee:||Allen, Eric E., Hastings, Phillip A., Nizet, Victor, Vacquier, Victor D.|
|School:||University of California, San Diego|
|School Location:||United States -- California|
|Source:||DAI-B 72/12, Dissertation Abstracts International|
|Subjects:||Genetics, Evolution and Development, Bioinformatics|
|Keywords:||Acute phase response, C1q, Evolution, Innate immune, Sghc1q, Zebrafish|
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