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Surfing the dynamics in genomes: Regulation of moved genes in Drosophila and the expansion of an apoptosis regulatory gene family in eukaryotes

Posted on:2011-03-01Degree:Ph.DType:Dissertation
University:Boston UniversityCandidate:Hu, LanFull Text:PDF
GTID:1440390002953407Subject:Biology
Abstract/Summary:
It is well accepted that genomes are dynamic. Genomes can be reorganized by gene duplications and chromosomal rearrangements. Gene duplications are mediated by either DNA- or RNA-based mechanisms. The latter give rise to retrotransposed genes (retrogenes) via reverse transcription from mRNA without the original regulation. Chromosomal rearrangements, while not normally generating duplicated copies, do move genes to new locations. The breakpoints of rearrangements can disrupt the regulatory region of nearby genes. Thus the functional expression of any retrotransposed or moved genes raises the question as to how they are regulated after drastic changes in their genomic environment.;The twelve fully sequenced Drosophila genomes provide an excellent dataset to study the regulation of lineage-supported retrogenes and genes moved via chromosomal rearrangements. Orphan retrogenes, whose parental copies have been lost or have degenerated into pseudogenes, are a particular class of retrogenes studied here. The primary aim of this dissertation is to investigate the transcriptional regulatory signals associated with such retrotransposed and moved genes. An efficient computational approach based on the Branch-and-Bound algorithm is implemented to seek the most informative ordered common cis-regulatory elements among the orthologues of these genes. Such a comparison can identify the regulatory signals that are common to all or specific to either the parent or the moved copy. From the examples explored, I have proposed the mechanisms by which retrotransposed and moved genes could be regulated to carry out the original functions and thus be retained in their new genomic environments.;The second aim of the dissertation is to delineate the duplicative expansion of an apoptosis regulatory gene family in a wide spectrum of eukaryote genomes. Most of these genes are currently unannotated or have been subsumed under two questionably related gene families. A detailed sequence and phylogenetic analysis shows that only five of them form a clear and unique gene family, which I named Lifeguard (LFG). My analysis provides information for understanding the specific biological roles of these proteins across a wide range of tissues in model organisms. The evolutionary relationships among LFG genes can provide a powerful prospect for extrapolating to human conditions.
Keywords/Search Tags:Gene, Genomes, Regulatory, Chromosomal rearrangements, Regulation
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