Avoiding organelle mutational meltdown across eukaryotes with or without a germline bottleneck

Edwards, David M. and Røyrvik, Ellen C. and Chustecki, Joanna M. and Giannakis, Konstantinos and Glastad, Robert C. and Radzvilavicius, Arunas L. and Johnston, Iain G. and Kirkwood, Thomas B.L. (2021) Avoiding organelle mutational meltdown across eukaryotes with or without a germline bottleneck. PLOS Biology, 19 (4). e3001153. ISSN 1545-7885

[thumbnail of journal.pbio.3001153.pdf] Text
journal.pbio.3001153.pdf - Published Version

Download (2MB)

Abstract

Mitochondrial DNA (mtDNA) and plastid DNA (ptDNA) encode vital bioenergetic apparatus, and mutations in these organelle DNA (oDNA) molecules can be devastating. In the germline of several animals, a genetic “bottleneck” increases cell-to-cell variance in mtDNA heteroplasmy, allowing purifying selection to act to maintain low proportions of mutant mtDNA. However, most eukaryotes do not sequester a germline early in development, and even the animal bottleneck remains poorly understood. How then do eukaryotic organelles avoid Muller’s ratchet—the gradual buildup of deleterious oDNA mutations? Here, we construct a comprehensive and predictive genetic model, quantitatively describing how different mechanisms segregate and decrease oDNA damage across eukaryotes. We apply this comprehensive theory to characterise the animal bottleneck with recent single-cell observations in diverse mouse models. Further, we show that gene conversion is a particularly powerful mechanism to increase beneficial cell-to-cell variance without depleting oDNA copy number, explaining the benefit of observed oDNA recombination in diverse organisms which do not sequester animal-like germlines (for example, sponges, corals, fungi, and plants). Genomic, transcriptomic, and structural datasets across eukaryotes support this mechanism for generating beneficial variance without a germline bottleneck. This framework explains puzzling oDNA differences across taxa, suggesting how Muller’s ratchet is avoided in different eukaryotes.

Item Type: Article
Subjects: Journal Eprints > Biological Science
Depositing User: Managing Editor
Date Deposited: 24 Jan 2023 05:37
Last Modified: 07 Mar 2024 07:58
URI: http://repository.journal4submission.com/id/eprint/799

Actions (login required)

View Item
View Item