Date of Award

1-1-2022

Language

English

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Biological Sciences

Content Description

1 online resource (iii, 19 pages) : illustrations (some color)

Dissertation/Thesis Chair

Thomas Begley

Committee Members

Andrew Berglund, Gabriele Fuchs

Keywords

Codon Usage, Fruit Fly, Human, Mitochondria, Mouse, Yeast, Transfer RNA, Gene expression, Mitochondrial pathology

Subject Categories

Biology

Abstract

The human mitochondrial genome is circular and encodes for its own two ribosomal RNAs, 22 tRNAs and 13 proteins needed for oxidative phosphorylation. Although the mitochondria require nuclear proteins and machinery for transcription and translation, the translation of 13 mRNAs occurs within the mitochondria. The dysregulation of mitochondrial translation is associated with diseases like MELAS (Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) and MERRF (Myoclonic epilepsy with ragged-red fibers), which can be caused by tRNA defects and lead to decreased translation of mitochondrial complex I proteins (MELAS). We have analyzed the codon usage of human mitochondrial genes and compared them to themselves and to nuclear counterparts using normalized Z-scores. We have determined that the codon usage in mitochondrial gene MT-ND6 (NADH dehydrogenase 6), a subunit of complex I, is opposite to the codon usage of all other mitochondrial genes. Codon analytics of mouse mitochondrial genes was also performed, and we observed a similar trend of opposing codon usage relative to other mitochondrial genes in mouse MT-ND6. When comparing to nuclear encoded genes, both mouse and human mitochondrial genes overused the codon LeuCTA and underused GlnCAG. When comparing to nuclear genome, all four organisms (human, mouse, yeast, and fruit fly) mitochondrial genes had certain codons that were overused or underused across all genes. Understanding both the baseline codon usage patterns and codon bias in the mitochondria can be used to model mitochondrial translation and understand how tRNA defects could cause disease, and potentially be used to develop targeted therapeutics for patients with mitochondrial diseases

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