Mitochondrial DNA Variation and Selfish Propagation Following Experimental Bottlenecking in Two Distantly Related Caenorhabditis briggsae Isolates.

Josiah T Wagner,Dee R Denver,Suzanne Estes,Dana K Howe

doi:10.3390/genes11010077

Josiah T Wagner, Dee R Denver + Show 2 more

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https://doi.org/10.3390/genes11010077

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Abstract

Understanding mitochondrial DNA (mtDNA) evolution and inheritance has broad implications for animal speciation and human disease models. However, few natural models exist that can simultaneously represent mtDNA transmission bias, mutation, and copy number variation. Certain isolates of the nematode Caenorhabditis briggsae harbor large, naturally-occurring mtDNA deletions of several hundred basepairs affecting the NADH dehydrogenase subunit 5 (nduo-5) gene that can be functionally detrimental. These deletion variants can behave as selfish DNA elements under genetic drift conditions, but whether all of these large deletion variants are transmitted in the same preferential manner remains unclear. In addition, the degree to which transgenerational mtDNA evolution profiles are shared between isolates that differ in their propensity to accumulate the nduo-5 deletion is also unclear. We address these knowledge gaps by experimentally bottlenecking two isolates of C. briggsae with different nduo-5 deletion frequencies for up to 50 generations and performing total DNA sequencing to identify mtDNA variation. We observed multiple mutation profile differences and similarities between C. briggsae isolates, a potentially species-specific pattern of copy number dysregulation, and some evidence for genetic hitchhiking in the deletion-bearing isolate. Our results further support C. briggsae as a practical model for characterizing naturally-occurring mtgenome variation and contribute to the understanding of how mtgenome variation persists in animal populations and how it presents in mitochondrial disease states.

Highlights

Animals that rely on the mitochondrial electron transport chain (ETC) for generating the majority of their energy inherently depend upon functional mitochondria
The present study is the first to demonstrate mitochondrial DNA (mtDNA) copy number dynamics following MA in C. briggsae and we found that MA results in significantly lower mtDNA:nDNA ratios in both AF16 and ED3101 isolates, in contrast to the findings in C. elegans (Figure 5)
We found that some mtDNA homopolymer indel mutations were prone to evolution across both isolates

Summary

Introduction

Animals that rely on the mitochondrial electron transport chain (ETC) for generating the majority of their energy inherently depend upon functional mitochondria. These intracellular organelles are unique because they harbor and replicate their own genomes that encode for several essential ETC subunits and components for intramitochondrial protein synthesis [1]. Direct and indirect measurements of mitochondrial genome (mtgenome) evolution in animals have suggested elevated per generation rates of mtgenome mutation when compared to nuclear DNA (nDNA) [2,3,4,5]. Single cells or organisms can harbor mtgenome copies of differing sequence, a phenomenon known as mtDNA heteroplasmy, which may be exacerbated by the accelerated mutation rate of mtDNA. Evolution can favor transmission of some deleterious mtDNA variants provided they have replication or transmission advantages compared to other mtDNA variants

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