This research was funded by National Institutes of Health grant number GM087628 to D.R.D and National Science Foundation grant number MCB-1330427 to S.E. The APC was funded by Cancer Early Detection Advanced Research (CEDAR) center, Oregon Health & Science University Knight Cancer Institute. J.T.W. is supported by funding from CEDAR.
Mitochondria DNA, Heteroplasmy -- Research
Understanding mitochondrial DNA (mtDNA) evolution and inheritance has broad implications for animal speciation and human disease models. However, few natural models exist that cansimultaneously 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 base pairs 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 dier 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.
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Locate the Document
Wagner, J. T., Howe, D. K., Estes, S., & Denver, D. R. (2020). Mitochondrial DNA Variation and Selfish Propagation Following Experimental Bottlenecking in Two Distantly Related Caenorhabditis briggsae Isolates. Genes, 11(1), 77.