Type of Document Dissertation Author Srikanta, Deepa Latha Author's Email Address email@example.com, firstname.lastname@example.org URN etd-11022009-153636 Title Non-Canonical Retrotransposon Insertions: Alternative Pathways to Integration Degree Doctor of Philosophy (Ph.D.) Department Biological Sciences Advisory Committee
Advisor Name Title Batzer, Mark Committee Chair Donze, David Committee Member Whitehead, Andrew Committee Member Wilson, Vincent Committee Member Crowe, William Dean's Representative Keywords
- insertion mechanisms
- Alu elements
Date of Defense 2009-10-28 Availability unrestricted AbstractThe majority of retrotransposons, mobile elements which move around the genome using an RNA intermediate, insert into their host genomes using target-primed reverse transcription (TPRT). Two of the most well-studied types of active retrotransposons in primates are L1s (Long Interspersed Element-1) and Alu elements. Both preferentially insert using TPRT, and these insertions can create genomic rearrangements and contribute to genome fluidity. Recent analyses have shown that L1s and Alu elements can insert using a variety of non-canonical mechanisms, including a DNA double-strand break repair pathway. Increased understanding of the mechanisms by which mobile elements insert into host genomes can help us examine why they are tolerated.
We surveyed non-canonical insertions using the human, chimpanzee, orangutan, rhesus, and marmoset genomes. Using both computational data mining and experimental verification, we have attempted to provide clear examples of the different mechanisms for these insertions and discuss their implications. In the first analysis, we assessed 23 non-classical Alu element insertions into primate genomes. These insertions left characteristic atypical sequence hallmarks since they did not use the typical L1 endonuclease cleavage site to insert into the host genomes. Mobile elements are largely considered disruptive to genomes, creating instability, but also generating diversity. In relatively rare cases, such as non-classical insertions, mobile elements may play a positive role in genomic stability by patching DNA double-strand breaks. Next, we examined both L1 and Alu elements in the context of internally primed insertions, resulting in characteristics similar to, but distinguishable from, classical TPRT. These twenty insertions provided support for the suggested lack of fidelity attributed to reverse transcriptase. We then characterized thirty-nine loci in our third analysis, which appear to have resulted from a variant of twin priming, itself a permutation of classical TPRT. The mechanisms by which mobile elements insert can offer insight on how mobile elements evade host defenses. Though this research is limited to primate genomes, the resulting understanding of the mechanisms at work is applicable to retrotransposons in general.
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