A Naturally Heteroplasmic Clam Provides Clues about the Effects of Genetic Bottleneck on Paternal mtDNA

Abstract

Mitochondrial DNA (mtDNA) is present in multiple copies within an organism. Since these copies are not identical, a single individual carries a heterogeneous population of mtDNAs, a condition known as heteroplasmy. Several factors play a role in the dynamics of the within-organism mtDNA population: among them genetic bottlenecks, selection, and strictly maternal inheritance are known to shape the levels of heteroplasmy across mtDNAs. In Metazoa, the only evolutionarily stable exception to the strictly maternal inheritance of mitochondria is the doubly uniparental inheritance (DUI), reported in 100+ bivalve species. In DUI species there are two highly divergent mtDNA lineages, one inherited through oocyte mitochondria (F-type) and the other through sperm mitochondria (M-type). Having both parents contributing to the mtDNA pool of the progeny makes DUI a unique system to study the dynamics of mtDNA populations. Since in bivalves the spermatozoon has few mitochondria (4-5), M-type mtDNA faces a tight bottleneck during embryo segregation, one of the narrowest mitochondrial bottlenecks investigated so far. Here, we analyzed the F- and M-type mtDNA variability within individuals of the DUI species Ruditapes philippinarum, and we investigated for the first time the effects of such a narrow bottleneck affecting mtDNA populations. As a potential consequence of this narrow bottleneck, the M-type mtDNA shows a large variability in different tissues, a condition so pronounced that it leads to genotypes from different tissues of the same individual not to cluster together. We believe such results may help understanding the effect of low population size on mtDNA bottleneck.

Bioenergetic consequences of sex-specific mitochondrial DNA evolution

“…It is still largely unclear whether this phenotype might be adaptive for enhanced male functions, and we cannot exclude that the remodelled mitochondrial bioenergetics in DUI sperm might be maladaptive, resulting from perpetuate inefficient selection on DUI M-mtDNA. On that end, a recent comparison between M-type alleles found in sperm or in male soma of the DUI R. philippinarum revealed tissue-specific difference in allele frequency distribution, potentially as a result of different selective forces acting on male gonads and adductors (strong versus more relaxed selection) [50]. Overall, our results reinforce what was detected in previous studies [36][37][38], namely that the control of mitochondrial respiration at the terminus of the respiratory chain might be under strong selective pressures to potentially ensure appropriate metabolic regulation of M-type mitochondria in DUI species.…”

Lack of transcriptional coordination between mitochondrial and nuclear oxidative phosphorylation genes in the presence of two divergent mitochondrial genomes

“…The presence of M-type mtRNA in somatic tissues seems to vary across DUI species, for example 60% male somatic samples in U. peninsularis and 89.5% male somatic samples in V. ellipsiformis presented somatic transcription of M-type mt genes ( Breton et al, 2017 ). In R. philippinarum , previous work reported variable number of M-type DNA and RNA in somatic tissues, depending on the individual ( Ghiselli et al, 2011 ; Iannello et al, 2021 ; Milani et al, 2014 ). In this work, we found that M-type is barely transcribed in the somatic tissues of most males.…”

“…One possibility could be the narrower germline bottleneck of M-type mtDNA. Past studies indicated that the F-type mtDNA copy number in eggs is on average 10 times higher than the copy number of M-type mtDNA in sperm ( Ghiselli et al, 2011 ), and that the narrower genetic bottleneck in M-type mtDNA could lead to the segregation of mtDNA variants in different tissues, causing remarkable within-individual variation and therefore also higher variability between samples ( Iannello et al, 2021 ). Alternatively, the presence of high intermediate frequency alleles and positive Tajima’s D could be a signal of balancing selection.…”

New Perspectives on the Evolution of Within-Individual Genome Variation and Germline/Soma Distinction

“… Iannello et al (2021) investigate mitochondrial heteroplasmy in a bivalve species with doubly uniparental inheritance. Their results reveal pronounced differences in mitochondrial genotypes among different tissues, possibly as a result of a strong bottleneck early during development ( Iannello et al 2021) .…”