Nejvíce citovaný článek - PubMed ID 24910436
MtDNA segregation in heteroplasmic tissues is common in vivo and modulated by haplotype differences and developmental stage
The house mouse, Mus musculus, is a widely used animal model in biomedical research, with classical laboratory strains (CLS) being the most frequently employed. However, the limited genetic variability in CLS hinders their applicability in evolutionary studies. Wild-derived strains (WDS), on the other hand, provide a suitable resource for such investigations. This study quantifies genetic and phenotypic data of 101 WDS representing 5 species, 3 subspecies, and 8 natural Y consomic strains and compares them with CLS. Genetic variability was estimated using whole mtDNA sequences, the Prdm9 gene, and copy number variation at two sex chromosome-linked genes. WDS exhibit a large natural variation with up to 2173 polymorphic sites in mitogenomes, whereas CLS display 92 sites. Moreover, while CLS have two Prdm9 alleles, WDS harbour 46 different alleles. Although CLS resemble M. m. domesticus and M. m. musculus WDS, they differ from them in 10 and 14 out of 16 phenotypic traits, respectively. The results suggest that WDS can be a useful tool in evolutionary and biomedical studies with great potential for medical applications.
- MeSH
- alely MeSH
- divoká zvířata genetika MeSH
- druhová specificita MeSH
- fenotyp MeSH
- genetická variace * MeSH
- histonlysin-N-methyltransferasa genetika MeSH
- mitochondriální DNA genetika MeSH
- myši * genetika MeSH
- variabilita počtu kopií segmentů DNA MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši * genetika MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- histonlysin-N-methyltransferasa MeSH
- mitochondriální DNA MeSH
- prdm9 protein, mouse MeSH Prohlížeč
Mammalian genes were long thought to be constrained within somatic cells in most cell types. This concept was challenged recently when cellular organelles including mitochondria were shown to move between mammalian cells in culture via cytoplasmic bridges. Recent research in animals indicates transfer of mitochondria in cancer and during lung injury in vivo, with considerable functional consequences. Since these pioneering discoveries, many studies have confirmed horizontal mitochondrial transfer (HMT) in vivo, and its functional characteristics and consequences have been described. Additional support for this phenomenon has come from phylogenetic studies. Apparently, mitochondrial trafficking between cells occurs more frequently than previously thought and contributes to diverse processes including bioenergetic crosstalk and homeostasis, disease treatment and recovery, and development of resistance to cancer therapy. Here we highlight current knowledge of HMT between cells, focusing primarily on in vivo systems, and contend that this process is not only (patho)physiologically relevant, but also can be exploited for the design of novel therapeutic approaches.
- MeSH
- energetický metabolismus MeSH
- fylogeneze MeSH
- mitochondrie * metabolismus MeSH
- nádory * genetika metabolismus MeSH
- savci MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- komentáře MeSH
- práce podpořená grantem MeSH
Vital mitochondrial DNA (mtDNA) populations exist in cells and may consist of heteroplasmic mixtures of mtDNA types. The evolution of these heteroplasmic populations through development, ageing, and generations is central to genetic diseases, but is poorly understood in mammals. Here we dissect these population dynamics using a dataset of unprecedented size and temporal span, comprising 1947 single-cell oocyte and 899 somatic measurements of heteroplasmy change throughout lifetimes and generations in two genetically distinct mouse models. We provide a novel and detailed quantitative characterisation of the linear increase in heteroplasmy variance throughout mammalian life courses in oocytes and pups. We find that differences in mean heteroplasmy are induced between generations, and the heteroplasmy of germline and somatic precursors diverge early in development, with a haplotype-specific direction of segregation. We develop stochastic theory predicting the implications of these dynamics for ageing and disease manifestation and discuss its application to human mtDNA dynamics.
- MeSH
- datové soubory jako téma MeSH
- genom mitochondriální genetika MeSH
- haplotypy genetika MeSH
- mitochondriální DNA genetika MeSH
- mitochondrie metabolismus MeSH
- modely u zvířat MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- oocyty cytologie imunologie MeSH
- variabilita počtu kopií segmentů DNA genetika MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- mitochondriální DNA MeSH
Being subject to intense post-copulatory selection, sperm size is a principal determining component of male fitness. Although previous studies have presented comparative sperm size data at higher taxonomic levels, information on the evolution of sperm size within species is generally lacking. Here, we studied two house mouse subspecies, Mus musculus musculus and Mus musculus domesticus, which undergo incipient speciation. We measured four sperm dimensions from cauda epididymis smears of 28 wild-caught mice of both subspecies. As inbred mouse strains are frequently used as proxies for exploring evolutionary processes, we further studied four wild-derived inbred strains from each subspecies. The subspecies differed significantly in terms of sperm head length and midpiece length, and these differences were consistent for wild mice and wild-derived strains pooled over genomes. When the inbred strains were analyzed individually, however, their strain-specific values were in some cases significantly shifted from subspecies-specific values derived from wild mice. We conclude that: (1) the size of sperm components differ in the two house mouse subspecies studied, and that (2) wild-derived strains reflect this natural polymorphism, serving as a potential tool to identify the genetic variation driving these evolutionary processes. Nevertheless, we suggest that more strains should be used in future experiments to account for natural variation and to avoid confounding results due to reduced variability and/or founder effect in the individual strains.
- MeSH
- genetická variace MeSH
- inbrední kmeny myší MeSH
- myši MeSH
- spermie cytologie MeSH
- vznik druhů (genetika) * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH