Paternal transmission of mitochondrial DNA as an integral part of mitochondrial inheritance in metapopulations of Drosophila simulans

Maternal inheritance is one of the hallmarks of animal mitochondrial DNA (mtDNA) and central to its success as a molecular marker. This mode of inheritance and subsequent lack of heterologous recombination allows us to retrace evolutionary relationships unambiguously down the matriline and without the confounding effects of recombinant genetic information. Accumulating evidence of biparental inheritance of mtDNA (paternal leakage), however, challenges our current understanding of how this molecule is inherited. Here, using Drosophila simulans collected from an East African metapopulation exhibiting recurring mitochondrial heteroplasmy, we conducted single fly matings and screened F1 offspring for the presence of paternal mtDNA using allele-specific PCR assays (AS–PCR). In all, 27 out of 4092 offspring were identified as harboring paternal mtDNA, suggesting a frequency of 0.66% paternal leakage in this species. Our findings strongly suggest that recurring mtDNA heteroplasmy as observed in natural populations of Drosophila simulans is most likely caused by repeated paternal leakage. Our findings further suggest that this phenomenon to potentially be an integral part of mtDNA inheritance in these populations and consequently of significance for mtDNA as a molecular marker.     

Dynamics of mitochondrial inheritance in the evolution of binary mating types and two sexes

The uniparental inheritance (UPI) of mitochondria is thought to explain the evolution of two mating types or even true sexes with anisogametes. However, the exact role of UPI is not clearly understood. Here, we develop a new model, which considers the spread of UPI mutants within a biparental inheritance (BPI) population. Our model explicitly considers mitochondrial mutation and selection in parallel with the spread of UPI mutants and self-incompatible mating types. In line with earlier work, we find that UPI improves fitness under mitochondrial mutation accumulation, selfish conflict and mitonuclear coadaptation. However, we find that as UPI increases in the population its relative fitness advantage diminishes in a frequency-dependent manner. The fitness benefits of UPI ‘leak’ into the biparentally reproducing part of the population through successive matings, limiting the spread of UPI. Critically, while this process favours some degree of UPI, it neither leads to the establishment of linked mating types nor the collapse of multiple mating types to two. Only when two mating types exist beforehand can associated UPI mutants spread to fixation under the pressure of high mitochondrial mutation rate, large mitochondrial population size and selfish mutants. Variation in these parameters could account for the range of UPI actually observed in nature, from strict UPI in some Chlamydomonas species to BPI in yeast. We conclude that UPI of mitochondria alone is unlikely to have driven the evolution of two mating types in unicellular eukaryotes.     

Small sperm,uniparental inheritance and selfish cytoplasmic elements: a comparison of two models

It has previously been suggested that small sperm size may be an adaptation to achieve uniparental inheritance of organelles, and hence to prevent the spread of selfish cytoplasmic elements. Such an explanation for anisogamy implies a mechanism whereby the male gamete eliminates its own cytoplasm prior to fusion with the egg. A model has been presented demonstrating the invasion and persistence of a modifier that acts gametically to kill its own organelles. Here we show, however, that this model is far from robust; indeed, if any cost is associated with the modifier it cannot persist. We also show that despite an empirically demonstrated association between anisogamy and multicellularity, this result also applies if the analysis is applied in the multicellular case. This class of model contrasts with the majority of analyses in which the modifier kills off the incoming gamete’s organelles. We show that these models are highly robust, even if uniparental inheritance is imperfect.     

Paternal inheritance of mitochondrial DNA in the sheep ( Ovine aries )

Paternal inheritance of mitochondria DNA in sheep was discovered by examination of 152 sheep from 38 hybrid families for mtDNA D-loop polymorphisms using PCR-RFLP, amplification of repeated sequence somain, and PCR-SSCP of the D-loop 5′ end region of a 253 bp fragment. Our findings have provided the first evidence of paternal inheritance of mtDNA in sheep and possible mechanisms of paternal inheritance were discussed.     

Paternal inheritance of mitochondrial DNA in the sheep (Ovine aries)

Paternal inheritance of mitochondria DNA in sheep was discovered by examination of 152 sheep from 38 hybrid families for mtDNA D-loop polymorphisms using PCR-RFLP, amplification of repeated sequence somain, and PCR-SSCP of the D-loop 5' end region of a 253 bp fragment. Our findings have provided the first evidence of paternal inheritance of mtDNA in sheep and possible mechanisms of paternal inheritance were discussed.     

Patterns of polymorphism and gene flow of gender-associated mitochondrial DNA lineages in European mussel populations

Mussels of the genus Mytilus have two types of mitochondrial DNA (mtDNA). The M type is transmitted paternally and the F type is transmitted maternally. RFLP analysis is used to assess phylogenetic relationships and nucleotide diversity and divergence for both mtDNA genomes in European populations of M. edulis and Atlantic and Mediterranean forms of M. galloprovincialis. Ten restriction endonucleases were used to assay variation in regions of the ND2 and COIII genes for a total of 77 individuals. F and M genomes show a concordant phylogenetic split into two major divergent clades, one specific to Mediterranean M. galloprovincialis and the other containing haplotypes from the three taxa. For both genomes, the geographical distribution of mtDNA variation suggests: (i) extensive levels of mtDNA introgression; (ii) asymmetric mtDNA gene flow from Atlantic to Mediterranean populations; and (iii) recurrent historical hybridization events. Significantly higher mtDNA diversity and divergence are observed for the M than F genome in all three Mytilus taxa, although the evolutionary forces responsible for these differences cannot be resolved. The extensive mtDNA gene flow between European Mytilus taxa conflicts with the restricted mtDNA introgression observed in American mussels , implying geographical variation in the nature of nuclear/mtDNA interactions regulating biparental inheritance.     

Nonhomologous Recombination Between the Large Unassigned Region of the Male and Female Mitochondrial Genomes in the Mussel, Mytilus trossulus

Doubly uniparental inheritance of mtDNA (DUI) is commonly observed in several genera of bivalves. Under DUI, female offspring inherit mtDNA from their mothers, while male offspring inherit mtDNA from both parents but preferentially transmit the paternally inherited mtDNA to their sons. Several studies have shown that the female- and male-specific mtDNA lineages in blue mussels, Mytilus spp., vary by upward of 20% at the nucleotide level. In addition to high levels of nucleotide substitution, the present study observed substantial gender-based length polymorphism in the presumptive mitochondrial control region (=large unassigned region; LUR) of North American M. trossulus. In this species, female lineage LUR haplotypes are over 2 kb larger than male lineage LUR haplotypes. Analysis of sequence data for these length variants indicates that the F LUR haplotypes of North American M. trossulus contain sequences similar to the F lineage control region in the congeners M. edulis and M. galloprovincialis. Relative to the F LUR in the latter two species, however, the F lineage LUR haplotypes in M. trossulus contain two large sequence insertions, each nearly 1 kb in size. One of these insertions has high sequence similarity to the male lineage LUR of M. trossulus. The tandem arrangement of F and M control region sequences in the F lineage LUR of M. trossulus is most likely the result of nonhomologous recombination between the male and the female mitochondrial genomes in M. trossulus, a finding that has important implications regarding the transmission and evolution of blue mussel mitochondrial genomes. [Reviewing Editor: Dr. Martin Kreitman]     

Why are most organelle genomes transmitted maternally?

Why the DNA‐containing organelles, chloroplasts, and mitochondria, are inherited maternally is a long standing and unsolved question. However, recent years have seen a paradigm shift, in that the absoluteness of uniparental inheritance is increasingly questioned. Here, we review the field and propose a unifying model for organelle inheritance. We argue that the predominance of the maternal mode is a result of higher mutational load in the paternal gamete. Uniparental inheritance evolved from relaxed organelle inheritance patterns because it avoids the spread of selfish cytoplasmic elements. However, on evolutionary timescales, uniparentally inherited organelles are susceptible to mutational meltdown (Muller's ratchet). To prevent this, fall‐back to relaxed inheritance patterns occurs, allowing low levels of sexual organelle recombination. Since sexual organelle recombination is insufficient to mitigate the effects of selfish cytoplasmic elements, various mechanisms for uniparental inheritance then evolve again independently. Organelle inheritance must therefore be seen as an evolutionary unstable trait, with a strong general bias to the uniparental, maternal, mode.     

Variation in mutation rate and polymorphism among mitochondrial genes of Silene vulgaris

The prevailing wisdom of the plant mitochondrial genome is that it has very low substitution rates, thus it is generally assumed that nucleotide diversity within species will also be low. However, recent evidence suggests plant mitochondrial genes may harbor variable and sometimes high levels of within-species polymorphism, a result attributed to variance in the influence of selection. However, insufficient attention has been paid to the effect of among-gene variation in mutation rate on varying levels of polymorphism across loci. We measured levels of polymorphism in seven mitochondrial gene regions across a geographically wide sample of the plant Silene vulgaris to investigate whether individual mitochondrial genes accumulate polymorphisms equally. We found that genes vary significantly in polymorphism. Tests based on coalescence theory show that the genes vary significantly in their scaled mutation rate, which, in the absence of differences among genes in effective population size, suggests these genes vary in their underlying mutation rate. Further evidence that among-gene variance in polymorphism is due to variation in the underlying mutation rate comes from a significant positive relationship between the number of segregating sites and silent site divergence from an outgroup. Contrary to recent studies, we found unconvincing evidence of recombination in the mitochondrial genome, and generally confirm the standard model of plant mitochondria characterized by low substitution rates and no recombination. We also show no evidence of significant variation in the strength or direction of selection among genes; this result may be expected if there is no recombination. The present study provides some of the most thorough data on plant mitochondrial polymorphism, and provides compelling evidence for mutation rate variation among genes. The study also demonstrates the difficulty in establishing a null model of mitochondrial genome polymorphism, and thus the difficulty, in the absence of a comparative approach, in testing the assumption that low substitution rates in plant mitochondria lead to low polymorphism.     

Divergence, hybridization, and recombination in the mitochondrial genome of the human pathogenic yeast Cryptococcus gattii

The inheritance of mitochondrial genes and genomes are uniparental in most sexual eukaryotes. This pattern of inheritance makes mitochondrial genomes in natural populations effectively clonal. Here, we examined the mitochondrial population genetics of the emerging human pathogenic fungus Cryptococcus gattii . The DNA sequences for five mitochondrial DNA fragments were obtained from each of 50 isolates belonging to two evolutionary divergent lineages, VGI and VGII. Our analyses revealed a greater sequence diversity within VGI than that within VGII, consistent with observations of the nuclear genes. The combined analyses of all five gene fragments indicated significant divergence between VGI and VGII. However, the five individual genealogies showed different relationships among the isolates, consistent with recent hybridization and mitochondrial gene transfer between the two lineages. Population genetic analyses of the multilocus data identified evidence for predominantly clonal mitochondrial population structures within both lineages. Interestingly, there were clear signatures of recombination among mitochondrial genes within the VGII lineage. Our analyses suggest historical mitochondrial genome divergence within C. gattii , but there is evidence for recent hybridization and recombination in the mitochondrial genome of this important human yeast pathogen.     

DNA replication and strand asymmetry in prokaryotic and mitochondrial genomes

Different patterns of strand asymmetry have been documented in a variety of prokaryotic genomes as well as mitochondrial genomes. Because different replication mechanisms often lead to different patterns of strand asymmetry, much can be learned of replication mechanisms by examining strand asymmetry. Here I summarize the diverse patterns of strand asymmetry among different taxonomic groups to suggest that (1) the single-origin replication may not be universal among bacterial species as the endosymbionts Wigglesworthia glossinidia, Wolbachia species, cyanobacterium Synechocystis 6803 and Mycoplasma pulmonis genomes all exhibit strand asymmetry patterns consistent with the multiple origins of replication, (2) different replication origins in some archaeal genomes leave quite different patterns of strand asymmetry, suggesting that different replication origins in the same genome may be differentially used, (3) mitochondrial genomes from representative vertebrate species share one strand asymmetry pattern consistent with the strand-displacement replication documented in mammalian mtDNA, suggesting that the mtDNA replication mechanism in mammals may be shared among all vertebrate species, and (4) mitochondrial genomes from primitive forms of metazoans such as the sponge and hydra (representing Porifera and Cnidaria, respectively), as well as those from plants, have strand asymmetry patterns similar to single-origin or multi-origin replications observed in prokaryotes and are drastically different from mitochondrial genomes from other metazoans. This may explain why sponge and hydra mitochondrial genomes, as well as plant mitochondrial genomes, evolves much slower than those from other metazoans.     

Evolution of the mitochondrial genome: protist connections to animals, fungi and plants

The past decade has seen the determination of complete mitochondrial genome sequences from a taxonomically diverse set of organisms. These data have allowed an unprecedented understanding of the evolution of the mitochondrial genome in terms of gene content and order, as well as genome size and structure. In addition, phylogenetic reconstructions based on mitochondrial DNA (mtDNA)-encoded protein sequences have firmly established the identities of protistan relatives of the animal, fungal and plant lineages. Analysis of the mtDNAs of these protists has provided insight into the structure of the mitochondrial genome at the origin of these three, mainly multicellular, eukaryotic groups. Further research into mtDNAs of taxa ancestral and intermediate to currently characterized organisms will help to refine pathways and modes of mtDNA evolution, as well as provide valuable phylogenetic characters to assist in unraveling the deep branching order of all eukaryotes.     

Mitogenomic analysis of a 50-generation chicken pedigree reveals a rapid rate of mitochondrial evolution and evidence for paternal mtDNA inheritance

Mitochondrial genomes represent a valuable source of data for evolutionary research, but studies of their short-term evolution have typically been limited to invertebrates, humans and laboratory organisms. Here we present a detailed study of 12 mitochondrial genomes that span a total of 385 transmissions in a well-documented 50-generation pedigree in which two lineages of chickens were selected for low and high juvenile body weight. These data allowed us to test the hypothesis of time-dependent evolutionary rates and the assumption of strict maternal mitochondrial transmission, and to investigate the role of mitochondrial mutations in determining phenotype. The identification of a non-synonymous mutation in ND4L and a synonymous mutation in CYTB, both novel mutations in Gallus, allowed us to estimate a molecular rate of 3.13 × 10⁻⁷ mutations/site/year (95% confidence interval 3.75 × 10⁻⁸–1.12 × 10⁻⁶). This is substantially higher than avian rate estimates based upon fossil calibrations. Ascertaining which of the two novel mutations was present in an additional 49 individuals also revealed an instance of paternal inheritance of mtDNA. Lastly, an association analysis demonstrated that neither of the point mutations was strongly associated with the phenotypic differences between the two selection lines. Together, these observations reveal the highly dynamic nature of mitochondrial evolution over short time periods.     

Inheritance of chloroplast and mitochondrial genomes in pedunculate oak investigated with an efficient PCR method

The restriction patterns of two chloroplast fragments and one mitochondrial DNA fragment, amplified by PCR with universal primers, were studied to determine the mode of inheritance of these organelles in 143 progeny of five intraspecific crosses in pedunculate oak (Quercus robur L.). The results indicate that both genomes are maternally inherited, an observation which agrees with the commonly observed pattern of inheritance in angiosperms. They confirm that both chloroplast DNA and mitochondrial DNA can be used as a source of seed-specific markers for the study of the geographic structure of oaks. This is the first report of organelle inheritance within the Fagaceae, an important and widespread tree family.     

外源基因在转基因动物中遗传和表达的稳定性

转基因技术经过近半个世纪的发展,已成为当今生物技术研究的热点。近10多年来,与核移植技术的结合,转基因效率大大提高,携带有不同外源基因的不同种类的转基因动物迅速增加。但是,成功获得转基因动物并不是转基因动物研究的最终目的,如何利用转基因技术为人类的需求服务才是科研人员始终面对的课题。在畜牧生产领域,通过转基因技术培育家畜新品种是转基因技术应用的重要体现,在我国这方面已经引起了广泛关注。但迄今为止,外源基因在转基因动物中遗传和表达的稳定性仍然是亟待解决的问题,究其原因,这主要与位置效应、外源基因的表观遗传学修饰和遗传效率相关,文章结合目前的研究进展和本实验室的研究结果,从这3方面阐述其作用机制,期望为转基因动物遗传育种向产业化的迈进提供一定的理论探讨。     

Of circles, forks and humanity: Topological organisation and replication of mammalian mitochondrial DNA

The organisation of mammalian mitochondrial DNA (mtDNA) is more complex than usually assumed. Despite often being depicted as a simple circle, the topology of mtDNA can vary from supercoiled monomeric circles over catenanes and oligomers to complex multimeric networks. Replication of mtDNA is also not clear cut. Two different mechanisms of replication have been found in cultured cells and in most tissues: a strand-asynchronous mode involving temporary RNA coverage of one strand, and a strand-coupled mode rather resembling conventional nuclear DNA replication. In addition, a recombination-initiated replication mechanism is likely to be associated with the multimeric mtDNA networks found in human heart. Although an insight into the general principles and key factors of mtDNA organisation and maintenance has been gained over the last few years, there are many open questions regarding replication initiation, termination and physiological factors determining mtDNA organisation and replication mode. However, common themes in mtDNA maintenance across eukaryotic kingdoms can provide valuable lessons for future work.     

The complete nucleotide sequence and multipartite organization of the tobacco mitochondrial genome: comparative analysis of mitochondrial genomes in higher plants

Tobacco is a valuable model system for investigating the origin of mitochondrial DNA (mtDNA) in amphidiploid plants and studying the genetic interaction between mitochondria and chloroplasts in the various functions of the plant cell. As a first step, we have determined the complete mtDNA sequence of Nicotiana tabacum. The mtDNA of N. tabacum can be assumed to be a master circle (MC) of 430,597 bp. Sequence comparison of a large number of clones revealed that there are four classes of boundaries derived from homologous recombination, which leads to a multipartite organization with two MCs and six subgenomic circles. The mtDNA of N. tabacum contains 36 protein-coding genes, three ribosomal RNA genes and 21 tRNA genes. Among the first class, we identified the genes rps1 and rps14, which had previously been thought to be absent in tobacco mtDNA on the basis of Southern analysis. Tobacco mtDNA was compared with those of Arabidopsis thaliana, Beta vulgaris, Oryza sativa and Brassica napus. Since repeated sequences show no homology to each other among the five angiosperms, it can be supposed that these were independently acquired by each species during the evolution of angiosperms. The gene order and the sequences of intergenic spacers in mtDNA also differ widely among the five angiosperms, indicating multiple reorganizations of genome structure during the evolution of higher plants. Among the conserved genes, the same potential conserved nonanucleotide-motif-type promoter could only be postulated for rrn18-rrn5 in four of the dicotyledonous plants, suggesting that a coding sequence does not necessarily move with the promoter upon reorganization of the mitochondrial genome.Electronic Supplementary Material Supplementary material is available in the online version of this article at Communicated by R. Hagemann     

Random chloroplast segregation and mitochondrial genome recombination in somatic hybrid plants of Diplotaxis catholica+Brassica juncea

Detailed molecular analysis of the somatic hybrid plants of Diplotaxis catholica+B. juncea indicated random chloroplast segregation. One of the five hybrid plants analyzed derived its chloroplasts from D. catholica and two hybrids had chloroplasts of B. juncea origin. Two hybrid plants maintained mixed population of chloroplasts. The mitochondrial (mt) genomes of the fusion partners had undergone recombinations. Occurrence of fragments specific to both the parents in HindIII digestion followed by atp 9 probing, as in hybrid DJ5, provided evidence for intergenomic mitochondrial recombination between D. catholica and B. juncea. Similar mt genome organization in two hybrids (DJ3 and DJ6) suggested that intergenomic recombination may be preferred at specific sites. Hybrid DJ1 had about 70% similarity to D. catholica in mt genome organization. mt genomes of hybrids DJ2, 3, 5, and 6 differed from B. juncea by 14.3–28%. The significance of these novel mt genome organizations in developing novel male sterility systems is discussed. Received: 4 April 1997 / Revision received: 19 December 1997 / Accepted: 28 March 1998