Type of Document Dissertation Author Meyer, Thomas Joshua Author's Email Address email@example.com, firstname.lastname@example.org URN etd-11122010-175148 Title Retrotransposon-Mediated Genomic Dynamism Degree Doctor of Philosophy (Ph.D.) Department Biological Sciences Advisory Committee
Advisor Name Title Batzer, Mark A. Committee Chair Brumfield, Robb T. Committee Member Cormier, Stephania Committee Member Kim, Joomyeong Committee Member Henry, James Dean's Representative Keywords
- mobile elements
Date of Defense 2010-11-08 Availability restricted AbstractRetrotransposons, a class of mobile elements, generate new copies in host genomes using RNA intermediates and reverse transcribing new copies into new loci. As such, the copy numbers of many active retrotransposon families increase dramatically over time. For example, ~42% of the human genome is comprised of retrotransposon sequences. The insertion activity of these elements, and the high degree of identity existing between the copies, have been shown to significantly impact the structure and stability of genomes, contributing in various ways from exon shuffling to inversions and from non-allelic homologous recombination to altering gene regulation. The two most successful mobile element lineages in primate genomes are LINE-1 (Long Interspersed Element-1) and Alu elements. Full-length LINE-1, or L1, elements are >6,000 bp in length and possess open reading frames encoding their own mobilization enzymes. Alu elements are a primate-specific family of SINEs (Short Interspersed Elements) that are ~300 bp in length and must hijack the enzymatic machinery of L1s for their mobilization.
The mechanism by which most L1 and Alu insertions occur is called Target Primed Reverse Transcription (TPRT). The structure of an insertion can be examined to determine if it is the result of TPRT, and many examples exist of loci that inserted in non-canonical fashions. We computationally searched through all assembled primate genomes and identified a group of atypical L1 insertions, all of which were truncated with homopolymeric stretches of thymine at their 5’ ends within the target site duplications, but which otherwise showed hallmarks of TPRT. We propose two possible mechanisms whereby these insertions may be explained, a variant of twin priming and a mechanism we term dual priming.
Because most retrotransposon insertions are found in non-coding regions of genomes, they are essentially neutral with respect to natural selection. These elements, therefore, can serve as excellent markers for reconstructing phylogenetic relationships. Alu elements, in particular, have been very successful throughout the primate radiation. We computationally screened the complete, unassembled sequence of the Northern white-cheeked gibbon (Nomascus leucogenys leucogenys) to identify 132 gibbon-specific Alu insertions. These insertions were then used to reconstruct a robust genus-level phylogeny of family Hylobatidae.
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