Selfish Drive Can Trump Function When Animal Mitochondrial Genomes Compete

Abstract

Mitochondrial genomes compete for transmission from mother to progeny. We explored this competition by introducing a second genome into Drosophila melanogaster to follow transmission.Competitions between closely related genomes favored those functional in electron transport, resulting in a host-beneficial purifying selection 1 . Contrastingly, matchups between distant genomes often favored those with negligible, negative or lethal consequences, indicating selfish selection. Exhibiting powerful selfish selection, a genome carrying a detrimental mutation displaced a complementing genome leading to population death after several generations. In a different pairing, opposing selfish and purifying selection counterbalanced to give stable transmission of two genomes. Sequencing of recombinant mitochondrial genomes revealed that the non-coding region, containing origins of replication, governs selfish transmission. Uniparental inheritance prevents encounters between distantly related genomes. Nonetheless, within each maternal lineage, constant competition among sibling genomes selects for super-replicators. We suggest that this relentless competition drives positive selection promoting change in the sequences influencing transmission.Natural selection culls populations of compromising mutations and favors traits that enhance organismal fitness. Nuclear genes have a relatively uniform exposure to natural selection as a result of regimented replication and segregation. In contrast, unconstrained competition among multiple mitochondrial genomes creates alternative ways to select for fit genomes, as well as opportunities for selfish genomes to increase in abundance.In heteroplasmic lines of Drosophila, mitochondrial genomes harboring mutations detrimental to oxidative phosphorylation (OXPHOS) function suffered a transmission disadvantage, even when complemented by co-resident wild-type genomes. The resulting Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms 2 Correspondence to: Patrick H. O'Farrell, ofarrell@cgl.ucsf.edu. Accession CodesThe complete sequence of a recombinant mitochondrial genome (Supplementary Figure 1a) between the two parental genomes (ATP6[1] and mt:ND2 del1 + mt:CoI T300I ) was deposited in Genbank and given the following accession number: KU764535. Author Contributions Competing financial interestsThe authors declare no competing financial interests. [6][7][8] . In multicellular organisms, defective mitochondrial genomes carried in animals can also benefit from selfish drive to enhance their propagation 9-14 . HHS Public AccessTo study head-to-head competition between mitochondrial genomes, we used cytoplasmic transplantation to bypass uniparental inheritance, which normally prevents encounters between unrelated genomes. In the resulting heteroplasmic lines, purifying selection dominated competition ...

Germline selection shapes human mitochondrial DNA diversity

“…Here we show that the segregation of mtDNA heteroplasmy likely plays a role in shaping D-loop population polymorphisms by a mechanism operating within the female germline. Similar findings have been seen in Drosophila where D-loop variants 'selfishly' drive segregation favoring a specific mtDNA genotype(32). These observations have implications for the development of mitochondrial transfer techniques for preventing the inheritance of severe pathogenic mtDNA mutations in humans(33,34).…”

A Genome-wide Screen Reveals that Reducing Mitochondrial DNA Polymerase Can Promote Elimination of Deleterious Mitochondrial Mutations

“…Studies in several systems suggested that purifying selection in the female germline reduces transmission of detrimental mitochondrial mutations [1][2][3][4][5][6][7]. In contrast, some selfish genomes can take over despite a cost to host fitness [8][9][10][11][12][13]. Within individuals, the outcome of competition is therefore influenced by multiple selective forces.…”

243rd ENMC international workshop: Developing guidelines for management of reproductive options for families with maternally inherited mtDNA disease, Amsterdam, the Netherlands, 22–24 March 2019

“…The potential risks from "selfish" mtDNAs [35] might be reduced by haplotype matching, that is, using donors who harbour mtDNA that is closely related to the recipient. However, such a regime would be difficult to implement.…”