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Population genetics of the cytoplasm and the units of selection on mitochondrial DNA in Drosophila melanogaster

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Abstract

Biological variation exists across a nested set of hierarchical levels from nucleotides within genes to populations within species to lineages within the tree of life. How selection acts across this hierarchy is a long-standing question in evolutionary biology. Recent studies have suggested that genome size is influenced largely by the balance of selection, mutation and drift in lineages with different population sizes. Here we use population cage and maternal transmission experiments to identify the relative strength of selection at an individual and cytoplasmic level. No significant trends were observed in the frequency of large (L) and small (S) mtDNAs across 14 generations in population cages. In all replicate cages, new length variants were observed in heteroplasmic states indicating that spontaneous length mutations occurred in these experimental populations. Heteroplasmic flies carrying L genomes were more frequent than those carrying S genomes suggesting an asymmetric mutation dynamic from larger to smaller mtDNAs. Mother-offspring transmission of heteroplasmy showed that the L mtDNA increased in frequency within flies both between and within generations despite sampling drift of the same intensity as occurred in population cages. These results suggest that selection for mtDNA size is stronger at the cytoplasmic than at the organismal level. The fixation of novel mtDNAs within and between species requires a transient intracellular heteroplasmic stage. The balance of population genetic forces at the cytoplasmic and individual levels governs the units of selection on mtDNA, and has implications for evolutionary inference as well as for the effects of mtDNA mutations on fitness, disease and aging.

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Acknowledgments

This work was motivated by the fortuitous discovery of mtDNA length heteroplasmy in crickets while I was learning how to use mtDNA to study the Gryllus hybrid zone in Rick Harrisons’ lab (Harrison et al. 1985). The microcosm of competing mtDNAs in the cytoplasm seemed like too interesting a problem to pass up, even if it was far afield from the ecological genetics that was the focus of my PhD thesis. It was an exciting time to be in Rick’s lab, and I owe much to Rick in making graduate school seem like summer science camp. The cricket heteroplasmy raised many questions and it seemed logical to do a population cage experiment in Drosophila, which was initiated as a postdoc in Dick Lewontin’s lab in 1988. From there, flies seemed like the best system to study how mtDNA variation is related to organismal fitness, and thus another person was sucked into the Drosophila model. I would like to thank W. Anderson, E. Arnason, D. Dykhuisen, A. MacRae, T. Prout for helpful comments and K. Zvonar for help with the frequency estimates. An anonymous reviewer provided many helpful comments that significantly improved the manuscript. Supported by National Research Service Award GM12357 to DMR and Grant GM21179 to R. C. Lewontin from the NIH, and grants DEB-9120293 from the NSF, grant GM067862 from the NIH and grant AG027849 from the NIA to DMR.

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  1. Department of Ecology and Evolution, Brown University, Providence, RI, 02912, USA

    David M. Rand

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Correspondence to David M. Rand.

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Rand, D.M. Population genetics of the cytoplasm and the units of selection on mitochondrial DNA in Drosophila melanogaster . Genetica 139, 685–697 (2011). https://doi.org/10.1007/s10709-011-9576-y

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