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Title: Comparative genomics of noncoding DNA
Author: Manee, Manee
ISNI:       0000 0004 7656 3475
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2016
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High levels of primary sequence conservation are observed in many noncoding regions of eukaryotic genomes. These conserved noncoding elements (CNEs) have shown to be robust indicators of functionally constrained elements. Nevertheless, the function of only a small fraction of such CNEs is known and their role in genome biology remains largely a mystery. Comparative genomics analysis in model organisms can shed light on CNE function and evolution of noncoding DNA in general. Recently, it has been reported that short CNEs in the Drosophila genome are typically very AT-rich but have unusually high levels of GC content in a much larger (~500 bp) window around them. To understand whether these "side effects" are dependent on their CNE definition or are a more general feature of the Drosophila genome, we analysed base composition of CNEs from two different CNE detection methods. We found side effects are real, but are restricted to a subset of CNEs in the genome. An alternative hypothesis to explain the existence of CNEs is the mutational cold spot hypothesis. Previous work using SNPs was shown evidence that CNEs are not mutational cold spots. Here, non-reference transposable elements (TEs) were used to test cold spot hypothesis. A significant reduction in levels of non-reference TEs was found in intronic and intergenic CNEs compared to the expected number of insertions. TEs in intergenic CNEs were also found at lower allele frequencies than TEs in intergenic spacers. Furthermore, we used simulation to explore the effects of insertion/deletion (indel) evolution on noncoding DNA sequences with and without constrained noncoding elements. We assessed several indel-capable simulators to test expected outcomes with no selectively constrained elements. Simulations with constrained elements show that sequences grow in length even when the deletion rate is exactly the same as the insertion rate. This result can be interpreted as being due to purifying selection on CNEs acting to remove an excess of deletion over insertions. Together, the results presented here provide insights into the evolution of noncoding DNA in one of the most important model organisms.
Supervisor: Hubbard, Simon Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Drosophila Genome ; Noncoding DNA ; Conserved Noncoding Elements ; Transposable Elements