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Quantitative testing of the molecular evolution of the mammalian circular RNA locus CDR1/CDR1-as (ciRS-7)

Krencius, Angelique Kerensa Cossette (2021) Quantitative testing of the molecular evolution of the mammalian circular RNA locus CDR1/CDR1-as (ciRS-7). Masters thesis, Northern Arizona University.

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Non-coding RNAs hold important regulatory functions in cells, but little attention has been given to how these functions evolved. ciRS-7 (CDR1-as) is a circular non-coding RNA known to act as a “sponge” for microRNA (miRNA), allowing rapid changes to gene expression. Because it plays an important role in mammalian brain development, ciRS-7 is an ideal target to analyze for evolutionary conservation. In addition, its status as a natural antisense transcript to the protein-coding gene CDR1 allows both sequences to be tested independently. A modified version of the McDonald-Kreitman test (MKT) for directional selection was developed to test for conservation of the miRNA binding sites in ciRS-7, and the traditional form was used to test for protein sequence conservation in the CDR1 sequence. MKT testing indicated that strong negative selection is acting to preserve miRNA binding sites in ciRS-7, whereas no directional selection is occurring on the CDR1 gene. This suggests that the CDR1/ciRS-7 locus evolved as a functional non-coding RNA rather than as a protein-coding gene, and that the CDR1 protein may be an incidental product. As such, further study of the evolutionary history of non-coding RNAs should be pursued.

Item Type: Thesis (Masters)
Publisher’s Statement: © Copyright is held by the author. Digital access to this material is made possible by the Cline Library, Northern Arizona University. Further transmission, reproduction or presentation of protected items is prohibited except with permission of the author.
Keywords: CDR1-as; circular RNA; ciRS-7; molecular evolution; non-coding RNA
Subjects: Q Science > QP Physiology
MeSH Subjects: E Analytical,Diagnostic and Therapeutic Techniques and Equipment > E05 Investigative Techniques
NAU Depositing Author Academic Status: Student
Department/Unit: Graduate College > Theses and Dissertations
College of the Environment, Forestry, and Natural Sciences > Biological Sciences
Date Deposited: 02 Mar 2022 17:05
Last Modified: 02 Mar 2022 17:05
URI: https://openknowledge.nau.edu/id/eprint/5780

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