Understanding the Tissue‐Specific Transcriptional Effects of Mitochondrial Introgression in Drosophila

Abstract

Mitochondrial DNA (mtDNA) mutations are an important cause of inherited disease. According to the United Mitochondrial Disease Foundation, “every 30 minutes a child is born who will develop a mitochondrial disease by age 10”. Mitochondrial Replacement Therapy can be used as a form of in‐vitro fertilization in which mitochondria are moved from a third party donor to a recipient oocyte or embryo. This new therapy enables women with mtDNA mutations to have healthy children. However, little is known about the effects of placing mtDNA into a “foreign” nuclear background. This study uses Drosophila as a model system to investigate how an alternative mitochondrial genotype (Sm21;OreR) effects the nuclear and mitochondrial transcriptome in 3 tissues (head, abdomen, and thorax). The effect of sex on RNA expression in these samples is also investigated. Drosophila melanogaster and Drosophila simulans flies were mated and extensively backcrossed to produce a progeny with isogenic D. melanogaster nuclear genome and D. simulans mtDNA (away team). The transcriptional response of tissues was then examined by performing RNA‐Seq on triplicate biological replicates of male and female Sm21;OreR (away team) and control OreR;OreR (home team) flies. Using bash in Oscar systems RNA‐seq reads from these tissues were aligned to a D. melanogaster genomic map. RStudio was used to perform statistical tests (PCA, Volcano plots, Heatmaps) to measure transcriptional variation within the samples. Our preliminary findings indicate that tissue type and sex are the main drivers of transcriptional difference within these samples.