Metabolic remodelling associated with mtDNA: insights into the adaptive value of doubly uniparental inheritance of mitochondria

Mitochondria produce energy through oxidative phosphorylation (OXPHOS), which depends on the expression of both nuclear and mitochondrial DNA (mtDNA). In metazoans, a striking exception from strictly maternal inheritance of mitochondria is doubly uniparental inheritance (DUI). This unique system involves the maintenance of two highly divergent mtDNAs (F- and M-type, 8–40% of nucleotide divergence) associated with gametes, and occasionally coexisting in somatic tissues. To address whether metabolic differences underlie this condition, we characterized the OXPHOS activity of oocytes, spermatozoa, and gills of different species through respirometry. DUI species express different gender-linked mitochondrial phenotypes in gametes and partly in somatic tissues. The M-phenotype is specific to sperm and entails (i) low coupled/uncoupled respiration rates, (ii) a limitation by the phosphorylation system, and (iii) a null excess capacity of the final oxidases, supporting a strong control over the upstream complexes. To our knowledge, this is the first example of a phenotype resulting from direct selection on sperm mitochondria. This metabolic remodelling suggests an adaptive value of mtDNA variations and we propose that bearing sex-linked mitochondria could assure the energetic requirements of different gametes, potentially linking male-energetic adaptation, mitotype preservation and inheritance, as well as resistance to both heteroplasmy and ageing.

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A naturally heteroplasmic clam provides clues about the effects of genetic bottleneck on paternal mtDNA

Genome Biology and Evolution ◽

10.1093/gbe/evab022 ◽

2021 ◽

Author(s):

Mariangela Iannello ◽

Stefano Bettinazzi ◽

Sophie Breton ◽

Fabrizio Ghiselli ◽

Liliana Milani

Keyword(s):

Maternal Inheritance ◽

Ruditapes Philippinarum ◽

Uniparental Inheritance ◽

Single Individual ◽

Doubly Uniparental Inheritance ◽

Large Variability ◽

Unique System ◽

Multiple Copies ◽

First Time ◽

Different Tissues

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.

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Linking paternally inherited mtDNA variants and sperm performance

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2019.0177 ◽

2019 ◽

Vol 375 (1790) ◽

pp. 20190177 ◽

Cited By ~ 5

Author(s):

Stefano Bettinazzi ◽

Sugahendni Nadarajah ◽

Andréanne Dalpé ◽

Liliana Milani ◽

Pierre U. Blier ◽

...

Keyword(s):

Fertilization Success ◽

Direct Selection ◽

Uniparental Inheritance ◽

Doubly Uniparental Inheritance ◽

Adaptive Value ◽

Mitochondrial Genotype ◽

Mtdna Evolution ◽

Mtdna Variants ◽

The Impact ◽

Energy Pathways

Providing robust links between mitochondrial genotype and phenotype is of major importance given that mitochondrial DNA (mtDNA) variants can affect reproductive success. Because of the strict maternal inheritance (SMI) of mitochondria in animals, haplotypes that negatively affect male fertility can become fixed in populations. This phenomenon is known as ‘mother's curse’. Doubly uniparental inheritance (DUI) of mitochondria is a stable exception in bivalves, which entails two mtDNA lineages that evolve independently and are transmitted separately through oocytes and sperm. This makes the DUI mitochondrial lineages subject to different sex-specific selective sieves during mtDNA evolution, thus DUI is a unique model to evaluate how direct selection on sperm mitochondria could contribute to male reproductive fitness. In this study, we tested the impact of mtDNA variants on sperm performance and bioenergetics in DUI and SMI species. Analyses also involved measures of sperm performance following inhibition of main energy pathways and sperm response to oocyte presence. Compared to SMI, DUI sperm exhibited (i) low speed and linearity, (ii) a strict OXPHOS-dependent strategy of energy production, and (iii) a partial metabolic shift towards fermentation following egg detection. Discussion embraces the adaptive value of mtDNA variation and suggests a link between male-energetic adaptation, fertilization success and paternal mitochondria preservation. This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.

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Differential Segregation Patterns of Sperm Mitochondria in Embryos of the Blue Mussel (Mytilus edulis)

Genetics ◽

10.1093/genetics/166.2.883 ◽

2004 ◽

Vol 166 (2) ◽

pp. 883-894

Author(s):

Liqin Cao ◽

Ellen Kenchington ◽

Eleftherios Zouros

Keyword(s):

Mitochondrial Dna ◽

Mytilus Edulis ◽

Blue Mussel ◽

Uniparental Inheritance ◽

Male Gonad ◽

Doubly Uniparental Inheritance ◽

Organelle Genomes ◽

Somatic Tissues ◽

Tight Linkage ◽

Mitotracker Green

Abstract In Mytilus, females carry predominantly maternal mitochondrial DNA (mtDNA) but males carry maternal mtDNA in their somatic tissues and paternal mtDNA in their gonads. This phenomenon, known as doubly uniparental inheritance (DUI) of mtDNA, presents a major departure from the uniparental transmission of organelle genomes. Eggs of Mytilus edulis from females that produce exclusively daughters and from females that produce mostly sons were fertilized with sperm stained with MitoTracker Green FM, allowing observation of sperm mitochondria in the embryo by epifluorescent and confocal microscopy. In embryos from females that produce only daughters, sperm mitochondria are randomly dispersed among blastomeres. In embryos from females that produce mostly sons, sperm mitochondria tend to aggregate and end up in one blastomere in the two- and four-cell stages. We postulate that the aggregate eventually ends up in the first germ cells, thus accounting for the presence of paternal mtDNA in the male gonad. This is the first evidence for different behaviors of sperm mitochondria in developing embryos that may explain the tight linkage between gender and inheritance of paternal mitochondrial DNA in species with DUI.

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The distribution of male-transmitted and female-transmitted mitochondrial DNA types in somatic tissues of blue mussels: Implications for the operation of doubly uniparental inheritance of mitochondrial DNA

Genome ◽

10.1139/g98-081 ◽

1998 ◽

Vol 41 (6) ◽

pp. 818-824 ◽

Cited By ~ 74

Author(s):

Manuel A Garrido-Ramos ◽

Donald T Stewart ◽

Brent W Sutherland ◽

Eleftherios Zouros

Keyword(s):

Mitochondrial Dna ◽

Blue Mussel ◽

Uniparental Inheritance ◽

Doubly Uniparental Inheritance ◽

Dominant Type ◽

Blue Mussels ◽

Somatic Tissues ◽

Dna Types ◽

M Genome

We have examined the mitochondrial DNA (mtDNA) content of several somatic tissues from male and female individuals of the blue mussel, Mytilus edulis. As expected from the mode of doubly uniparental inheritance (DUI) of mtDNA that is characteristic of this genus, the dominant type of mtDNA in male gonads was the male-transmitted M type. In contrast, all male somatic tissues were dominated by the female-transmitted F type. The M type could occasionally be detected in one or another tissue of a few female individuals. The findings have several implications for the operation of doubly uniparental inheritance of mitochondrial DNA, among which the most important are (i) the M genome does not have an unconditional replicative advantage over the F genome, and (ii) in contrast to "masculinization" (the process by which an F molecule assumes the role of the M genome) "feminization" (the process by which an M molecule assumes the role of the F genome) might be a rare but not impossible phenomenon.Key words: mitochondrial DNA inheritance, mitochondrial DNA tissue distribution, blue mussels, gender-specific mtDNA, doubly uniparental inheritance of mtDNA, Mytilus.

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Presence of male mitochondria in somatic tissues and their functional importance at the whole animal level in the marine bivalve Arctica islandica

Communications Biology ◽

10.1038/s42003-021-02593-1 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Cyril Dégletagne ◽

Doris Abele ◽

Gernot Glöckner ◽

Benjamin Alric ◽

Heike Gruber ◽

...

Keyword(s):

Mitochondrial Genes ◽

Marine Bivalve ◽

Uniparental Inheritance ◽

Natural Occurrence ◽

Doubly Uniparental Inheritance ◽

Arctica Islandica ◽

Sharp Drop ◽

Respiratory Capacity ◽

Icelandic Population ◽

Somatic Tissues

AbstractMetazoans normally possess a single lineage of mitochondria inherited from the mother (♀-type mitochondria) while paternal mitochondria are absent or eliminated in fertilized eggs. In doubly uniparental inheritance (DUI), which is specific to the bivalve clade including the ocean quahog, Arctica islandica, ♂-type mitochondria are retained in male gonads and, in a few species, small proportions of ♂-type mitochondria co-exist with ♀-type in somatic tissues. To the best of our knowledge, we report, for the first time in metazoan, the natural occurrence of male and female individuals with exclusively ♂-type mitochondria in somatic tissues of the bivalve A. islandica. Mitochondrial genomes differ by ~5.5% at DNA sequence level. Exclusive presence of ♂-type mitochondria affects mitochondrial complexes partially encoded by mitochondrial genes and leads to a sharp drop in respiratory capacity. Through a combination of whole mitochondrial genome sequencing and molecular assays (gene presence and expression), we demonstrate that 1) 11% of individuals of an Icelandic population appear homoplasmic for ♂-type mitochondria in somatic tissues, 2) ♂-type mitochondrial genes are transcribed and 3) individuals with ♂-type mitochondria in somatic cells lose 30% of their wild-type respiratory capacity. This mitochondrial pattern in A. islandica is a special case of DUI, highlighted in individuals from both sexes with functional consequences at cellular and conceivably whole animal level.

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Tissue-specific expression of male-transmitted mitochondrial DNA and its implications for rates of molecular evolution in Mytilus mussels (Bivalvia: Mytilidae)

Genome ◽

10.1139/g01-159 ◽

2002 ◽

Vol 45 (2) ◽

pp. 348-355 ◽

Cited By ~ 50

Author(s):

Anne C Dalziel ◽

Donald T Stewart

Keyword(s):

Mitochondrial Dna ◽

Molecular Evolution ◽

Uniparental Inheritance ◽

Rt Pcr ◽

Male Gonad ◽

Doubly Uniparental Inheritance ◽

Specific Expression ◽

Somatic Tissues ◽

Selective Forces ◽

Rates Of Molecular Evolution

Mytilus and other bivalves exhibit an unusual system of mitochondrial DNA (mtDNA) transmission termed doubly uniparental inheritance (DUI). Specifically, males transmit the mtDNA they have received from their fathers to their sons. Females transmit their mother's mtDNA to both sons and daughters. Males are normally heteroplasmic and females are normally homoplasmic, but not exclusively. This system is associated with an unusual pattern of molecular evolution. Male-transmitted mtDNA (M type) evolves faster than female-transmitted (F type) mtDNA. Relatively relaxed selection on the M type has been proposed as an explanation for this phenomenon. To further evaluate the selective forces acting upon the M-type genome, we used RT-PCR to determine where it is expressed. M-type mtDNA expression was detected in all gonad samples and in 50% of somatic tissues of males, and in a single female tissue. F-type mtDNA expression was detected in all female tissues, all male somatic tissues, and all but one male gonad sample. We argue that the expression of M-type mtDNA in male somatic and male gonad tissues has implications for the strength of selection acting upon it.Key words: gender-associated mitochondrial DNA, doubly uniparental inheritance of mtDNA, Mytilus edulis, molecular evolution.

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Pursuing the quest for better understanding the taxonomic distribution of the system of doubly uniparental inheritance of mtDNA

PeerJ ◽

10.7717/peerj.2760 ◽

2016 ◽

Vol 4 ◽

pp. e2760 ◽

Cited By ~ 37

Author(s):

Arthur Gusman ◽

Sophia Lecomte ◽

Donald T. Stewart ◽

Marco Passamonti ◽

Sophie Breton

Keyword(s):

Maternal Inheritance ◽

Uniparental Inheritance ◽

Bivalve Species ◽

Animal Kingdom ◽

Doubly Uniparental Inheritance ◽

Taxonomic Distribution ◽

Scrobicularia Plana ◽

Mitochondrial Transmission ◽

And Function ◽

Yoldia Hyperborea

There is only one exception to strict maternal inheritance of mitochondrial DNA (mtDNA) in the animal kingdom: a system named doubly uniparental inheritance (DUI), which is found in several bivalve species. Why and how such a radically different system of mitochondrial transmission evolved in bivalve remains obscure. Obtaining a more complete taxonomic distribution of DUI in the Bivalvia may help to better understand its origin and function. In this study we provide evidence for the presence of sex-linked heteroplasmy (thus the possible presence of DUI) in two bivalve species, i.e., the nuculanoidYoldia hyperborea(Gould, 1841)and the veneroidScrobicularia plana(Da Costa,1778), increasing the number of families in which DUI has been found by two. An update on the taxonomic distribution of DUI in the Bivalvia is also presented.

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Bioenergetic consequences of sex-specific mitochondrial DNA evolution

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2021.1585 ◽

2021 ◽

Vol 288 (1957) ◽

pp. 20211585

Author(s):

Stefano Bettinazzi ◽

Liliana Milani ◽

Pierre U. Blier ◽

Sophie Breton

Keyword(s):

Mitochondrial Genome ◽

Acid Metabolism ◽

Maternal Inheritance ◽

Tricarboxylic Acid Cycle ◽

General Rule ◽

High Energy ◽

Uniparental Inheritance ◽

Doubly Uniparental Inheritance ◽

Antioxidant Metabolism ◽

The Impact

Doubly uniparental inheritance (DUI) represents a notable exception to the general rule of strict maternal inheritance (SMI) of mitochondria in metazoans. This system entails the coexistence of two mitochondrial lineages (F- and M-type) transmitted separately through oocytes and sperm, thence providing an unprecedented opportunity for the mitochondrial genome to evolve adaptively for male functions. In this study, we explored the impact of a sex-specific mitochondrial evolution upon gamete bioenergetics of DUI and SMI bivalve species, comparing the activity of key enzymes of glycolysis, fermentation, fatty acid metabolism, tricarboxylic acid cycle, oxidative phosphorylation and antioxidant metabolism. Our findings suggest reorganized bioenergetic pathways in DUI gametes compared to SMI gametes. This generally results in a decreased enzymatic capacity in DUI sperm with respect to DUI oocytes, a limitation especially prominent at the terminus of the electron transport system. This bioenergetic remodelling fits a reproductive strategy that does not require high energy input and could potentially link with the preservation of the paternally transmitted mitochondrial genome in DUI species. Whether this phenotype may derive from positive or relaxed selection acting on DUI sperm is still uncertain.

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Natural Heteroplasmy and Mitochondrial Inheritance in Bivalve Molluscs

Integrative and Comparative Biology ◽

10.1093/icb/icz061 ◽

2019 ◽

Vol 59 (4) ◽

pp. 1016-1032 ◽

Cited By ~ 8

Author(s):

Fabrizio Ghiselli ◽

Maria Gabriella Maurizii ◽

Arkadiy Reunov ◽

Helena Ariño-Bassols ◽

Carmine Cifaldi ◽

...

Keyword(s):

Developmental Stages ◽

Sequence Divergence ◽

Ruditapes Philippinarum ◽

Uniparental Inheritance ◽

Doubly Uniparental Inheritance ◽

Germline Development ◽

High Sequence Divergence ◽

High Amino Acid ◽

Somatic Tissues ◽

First Time

Abstract Heteroplasmy is the presence of more than one type of mitochondrial genome within an individual, a condition commonly reported as unfavorable and affecting mitonuclear interactions. So far, no study has investigated heteroplasmy at protein level, and whether it occurs within tissues, cells, or even organelles. The only known evolutionarily stable and natural heteroplasmic system in Metazoa is the Doubly Uniparental Inheritance (DUI)—reported so far in ∼100 bivalve species—in which two mitochondrial lineages are present: one transmitted through eggs (F-type) and the other through sperm (M-type). Because of such segregation, mitochondrial oxidative phosphorylation proteins reach a high amino acid sequence divergence (up to 52%) between the two lineages in the same species. Natural heteroplasmy coupled with high sequence divergence between F- and M-type proteins provides a unique opportunity to study their expression and assess the level and extent of heteroplasmy. Here, for the first time, we immunolocalized F- and M-type variants of three mitochondrially-encoded proteins in the DUI species Ruditapes philippinarum, in germline and somatic tissues at different developmental stages. We found heteroplasmy at organelle level in undifferentiated germ cells of both sexes, and in male soma, whereas gametes were homoplasmic: eggs for the F-type and sperm for the M-type. Thus, during gametogenesis, only the sex-specific mitochondrial variant is maintained, likely due to a process of meiotic drive. We examine the implications of our results for DUI proposing a revised model, and we discuss interactions of mitochondria with germ plasm and their role in germline development. Molecular and phylogenetic evidence suggests that DUI evolved from the common Strictly Maternal Inheritance, so the two systems likely share the same underlying molecular mechanism, making DUI a useful system for studying mitochondrial biology.

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