Bioinformatically-based identification of cis-regulatory elements / by Pooja Ranbirchand Sethi.
| Author/creator | Sethi, Pooja Ranbirchand author. |
| Other author | Stellwag, Edmund J. (Edmund Johannes), 1951- degree supervisor. |
| Other author | East Carolina University. Department of Biology. |
| Format | Theses and dissertations |
| Production | 2004. |
| Description | 94 leaves : illustrations (some color) ; 28 cm + 1 CD-ROM (4 3/4 in.) |
| Supplemental Content | Access via ScholarShip |
| Subjects |
| Summary | The recent availability of whole genome sequences has fueled the development of computational tools that are directed towards bioinformatics-based methods for identification of cis-regulatory elements. In this thesis, I describe a bioinformatics-based method that can be used for this purpose. This method, unlike previously developed methods, incorporates a direct measure of the effects of natural selection as a determinant factor in constraining sequence evolution in comparisons between non-protein coding sequences. As such, the method developed in this thesis provides a biologically relevant framework for comparisons of sequence evolution within the non-protein coding region of genomes and represents a departure from other methods that adopt a purely statistical or largely inferential approach to identification of putative cis-regulatory elements. Results of this method demonstrate that it correctly identifies functionally characterized cis-regulatory elements from the mouse {Mus musculus), which demonstrates its validity. Pair-wise comparisons conducted on aligned intergenic and intron sequences from orthologous horn shark (Heterodontus francisci), human (Homo sapiens), mouse (Mus musculus), bichir (Polypterus senegalus), striped bass (Morone saxatilis), tilapia (Oreochromis niloticus), pufferfish (Takifugu rubripes) and zebrafish (Danio rerio) HoxA cluster paralogous group 2 sequences revealed 3 sequence domains that are under purifying selection in all these species, indicative that these regions likely represent components of cis-regulatory control regions in the common ancestor to gnathostomes and fundamental to regulation of paralog group 2 Hox genes in general. In addition to these three domains, an in-depth analysis of one conserved sequence domain using mouse and striped bass HoxA as index sequences revealed the presence of4 gnathostome-specific elements, 2 Hox-cluster specific elements, 1 actinopterygian-specific element, 2 teleost HoxAa-specific elements, 69 perciformes-specific elements and 53 mammalian-specific elements. The results also showed the presence ofcis regulatory sequences in the sarcopterygian HoxA clusters that have been partitioned between the teleost HoxAa and HoxAb cluster sequences. These results indicate the presence of a lineage-specific pattern of putative cis-regulatory element evolution. Overall, the results demonstrate the applicability of this method for identification of putative cis-regulatory elements and underscore the value of including an unambiguous measure of sequence evolution as a parameter in computing the divergence between sequences in the non-protein coding genome. |
| General note | Presented to the faculty of the Department of Biology. |
| General note | Advisor: Edmund J. Stellwag |
| Dissertation note | M.S. East Carolina University 2004 |
| Bibliography note | Includes bibliographical references (leaves 74-87). |
| Genre/form | dissertations. |
| Genre/form | Academic theses. |
| Genre/form | Academic theses. |
| Genre/form | Thèses et écrits académiques. |
Availability
| Library | Location | Call Number | Status | Item Actions |
|---|---|---|---|---|
| Joyner | University Archives | ASK AT SPECIAL COLLECTIONS DESK | ✔ Available | Request Material |
| Electronic Resources | Access Content Online | ✔ Available |