During the last decades, mitochondria and their DNA have become a hot topic of research due to their essential roles which are necessary for cells survival and pathology.
In this study, multiple methods have been developed to help with the understanding
of mitochondrial DNA and its evolution. These methods tackle two essential problems in this area: the accurate annotation of protein-coding genes and mitochondrial genome rearrangements.
Mitochondrial genome sequences are published nowadays with increasing pace,
which creates the need for accurate and fast annotation tools that do not require
manual intervention. In this work, an automated pipeline for fast de-novo annotation of mitochondrial protein-coding genes is implemented. The pipeline includes methods for enhancing multiple sequence alignment, detecting frameshifts and building protein profiles guided by phylogeny. The methods are tested on animal mitogenomes available in RefSeq, the comparison with reference annotations highlights the high quality of the produced annotations. Furthermore, the frameshift method predicted a large number of frameshifts, many of which were unknown.
Additionally, an eficient partially-local alignment method to investigate genomic
rearrangements in mitochondrial genomes is presented in this study. The method
is novel and introduces a partially-local dynamic programming algorithm on three
sequences around the breakpoint region. Unlike the existing methods which study
the rearrangement at the genes order level, this method allows to investigate the
rearrangement on the molecular level with nucleotides precision. The algorithm is
tested on both artificial data and real mitochondrial genomic sequences. Surprisingly, a large fraction of rearrangements involve the duplication of local sequences. Since the implemented approach only requires relatively short parts of genomic sequence around a breakpoint, it should be applicable to non-mitochondrial studies as well.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:20973 |
| Date | 21 March 2018 |
| Creators | Al Arab, Marwa |
| Contributors | Universität Leipzig |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English, German |
| Detected Language | English |
| Type | info:eu-repo/semantics/updatedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | qucosa:21241 |
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