核内线粒体DNA片段(nuclear mitochondrial DNA segments,Numts)给线粒体DNA的研究和应用带来了严重干扰,因而备受广大学者的关注。国内外学者在Numts的检测方面做了大量的研究。尤其是近年来,随着大量基因组数据的积累,相关研究不再局...核内线粒体DNA片段(nuclear mitochondrial DNA segments,Numts)给线粒体DNA的研究和应用带来了严重干扰,因而备受广大学者的关注。国内外学者在Numts的检测方面做了大量的研究。尤其是近年来,随着大量基因组数据的积累,相关研究不再局限于研究特定线粒体基因的核内同源片段,而是拓展到基因组水平上比较不同物种的Numts含量和分布,物种内部Numts的多态性也日益被研究者重视。该文从Numts的形成机制、检测方法、数量和分布对线粒体DNA研究的干扰及排除方法等方面进行了总结与归纳,也对Numts的研究意义与未来的发展趋势进行了简要分析。展开更多
Mitochondrial DNA sequences transferred to the nucleus give rise to the so-called nuclear mitochondrial DNA （numt）. In the GenBank database, 244 numts have been found in six orders of birds （Anseriformes, Columbifo...Mitochondrial DNA sequences transferred to the nucleus give rise to the so-called nuclear mitochondrial DNA （numt）. In the GenBank database, 244 numts have been found in six orders of birds （Anseriformes, Columbiformes, Falconiformes, Charadriiformes, Galliformes and Passeriformes）. Sequences alignment （NCBI-BLASTN） was carded out with mitochondrial and corresponding nuclear genome sequences in nine vertebrate species. The sequences with high homology were considered as numts. The number of numts ranged from 15 in chicken to 159 in chimpanzee. The sequences of numts in macaque, chimpanzee, and human spanned 100% of the entire mammalian mitochondrial genome. The reconstructed frequency of the mitochondrial gene transferred to the nucleus demonstrated that the rRNA genes had high frequencies than other mitochondrial genes. Using the RepeatMasker program, the transposable elements were detected in the flanking regions of each numt. The results showed that less than 5% of the flanking sequences were made up of repetitive elements in chicken. The GC content of 5＇- and 3＇-flanking regions of numts in nine species was less than 44%. The analysis of the flanking sequences provided a valuable understanding for future study on mechanism of mitochondrial gene transfer to the nucleus and the site of numt integration.展开更多
In the human the peptide Humanin is produced from the small Humanin gene which is embedded as a gene-within-a-gene in the 16S ribosomal molecule of the mitochondrial DNA （mtDNA）. The peptide itself appears to be sig...In the human the peptide Humanin is produced from the small Humanin gene which is embedded as a gene-within-a-gene in the 16S ribosomal molecule of the mitochondrial DNA （mtDNA）. The peptide itself appears to be significant in the prevention of cell death in many tissues and improve cognition in animal models. By using simple data mining techniques, it is possible to show that 99.4% of the human Humanin sequences in the GenBank database are unaffected by mutations. However, in other vertebrates, pseudogenization of the Humanin gene is a common feature; occurring apparently randomly in some species and not others. The persistence, or loss, of a functional Humanin gene may be an important factor in laboratory animals, especially if they are being used as animal models in studies of Alzheimer＇s disease （AD）. The exact reason why Humanin underwent pseudogenization in some vertebrate species during their evolution remains to be determined. This study was originally planned to review the available information about Humanin and it was a surprise to be able to show that pseudogenization has occurred in a gene in the mtDNA and is not restricted solely to chromosomal genes.展开更多
The discovery of Paranthropus deyiremeda in 3.3 - 3.5 million-year-old fossil sites in Afar, together with 30% of the gorilla genome showing lineage sorting between humans and chimpanzees, and a NUMT (“nuclear mitoch...The discovery of Paranthropus deyiremeda in 3.3 - 3.5 million-year-old fossil sites in Afar, together with 30% of the gorilla genome showing lineage sorting between humans and chimpanzees, and a NUMT (“nuclear mitochondrial DNA segment”) on chromosome 5 that is shared by both gorillas, humans and chimpanzees, and shown to have diverged at the time of the Pan-Homo split rather than the Gorilla/Pan-Homo split, provides conclusive evidence that introgression from the gorilla lineage caused the Pan-Homo split, and the speciation of both the Australopithecus lineage and the Paranthropus lineage.展开更多
DNAs from the cytoplasmic genomes often communicate with the nuclear genome during regulation,development,and evolution.However,the dynamics of cytonuclear interaction during crop domestication have still been rarely ...DNAs from the cytoplasmic genomes often communicate with the nuclear genome during regulation,development,and evolution.However,the dynamics of cytonuclear interaction during crop domestication have still been rarely investigated.Here,we examine cytonuclear interactions during grapevine domestication using pan-mitogenome,pan-plastome,and haplotype-resolved nuclear genomes,all assembled from long-read sequences across 33 wild and domesticated grapevine accessions.Structural variation shaped the mitogenomic variation in gene contents,leading to duplications of three specific genes during grapevine domestication(one cox and two rpl genes).Extensive genomic signals of cytonuclear interactions were detected,including a total of212–431 nuclear–mitochondrial segments(NUMTs)and 95–205 nuclear–plastid segments(NUPTs).These results showed that NUMTs were under strong selection and were more abundant in cultivated grapes,whereas NUPTs dominated in wild grapes,indicating the evolutionary trajectories of cytonuclear interactions during grape domestication.Through Genome-Wide Association Study(GWAS),we identified 84 candidate genes associated with mitochondrial–nuclear genome interactions.Among these,the PFD1 gene acts as a signaling regulator,modulating specific signaling pathways regulated by the mitochondria.Interestingly,there are significantly more cytonuclear interaction genes near NUMTs than in other genomic regions,suggesting NUMTmediated interactions between the nuclear and mitochondrial genomes.Overall,our study provides evidence that NUMTs promote cytonuclear interaction during grapevine domestication,offering new insight into the impact of cytonuclear interactions on plant evolution,genetics,and breeding.展开更多
Human mitochondrial DNA(mt DNA)harbors essential mutations linked to aging,neurodegenerative diseases,and complex muscle disorders.Due to its uniparental and haploid inheritance,mt DNA captures matrilineal evolutionar...Human mitochondrial DNA(mt DNA)harbors essential mutations linked to aging,neurodegenerative diseases,and complex muscle disorders.Due to its uniparental and haploid inheritance,mt DNA captures matrilineal evolutionary trajectories,playing a crucial role in population and medical genetics.However,critical questions about the genomic diversity patterns,inheritance models,and evolutionary and medical functions of mt DNA remain unresolved or underexplored,particularly in the transition from traditional genotyping to largescale genomic analyses.This review summarizes recent advancements in data-driven genomic research and technological innovations that address these questions and clarify the biological impact of nuclear-mitochondrial segments(NUMTs)and mt DNA variants on human health,disease,and evolution.We propose a streamlined pipeline to comprehensively identify mt DNA and NUMT genomic diversity using advanced sequencing and computational technologies.Haplotype-resolved mt DNA sequencing and assembly can distinguish authentic mt DNA variants from NUMTs,reduce diagnostic inaccuracies,and provide clearer insights into heteroplasmy patterns and the authenticity of paternal inheritance.This review emphasizes the need for integrative multi-omics approaches and emerging long-read sequencing technologies to gain new insights into mutation mechanisms,the influence of heteroplasmy and paternal inheritance on mt DNA diversity and disease susceptibility,and the detailed functions of NUMTs.展开更多
The transfer of mitochondrial DNA to the nuclear genome gives rise to the nuclear DNA sequences of mitochon-drial origin(NUMTs),considered as a driving force in genome evolution.In this study,NUMTs in 23 bat genomes w...The transfer of mitochondrial DNA to the nuclear genome gives rise to the nuclear DNA sequences of mitochon-drial origin(NUMTs),considered as a driving force in genome evolution.In this study,NUMTs in 23 bat genomes were investigated and compared systematically.The results showed that NUMTs existed in 22 genomes except for Noctilio leporinus,suggesting that mitochondrial fragment insertion in the nuclear genome was a common event in bat genomes.However,remarkable variations in NUMTs number,cumulative length,and proportion in the nu-clear genome were discovered across bat species.Further orthologous NUMT loci analysis of the Phyllostomidae family indicated that the NUMTs insertion events in bat genomes were homoplasy-free.The NUMTs were mainly inserted into the intergenic regions,particularly,co-localized with repetitive sequences(especially transposable el-ements).However,several NUMTs were inserted into genes,some of which were in the exon region of functional genes.One NUMT in the genome of Pteropus alecto surprisingly matched with cDNA of ATP8B3 that provided evidence of NUMTs with coding function.Phylogenic analysis on NUMTs originating from COXI and COXII loci highlighted 2 clusters of Yinpterochiroptera and Yangochiroptera for Chiroptera.Seven NUMTs from Rhinolophus ferrumequinum were amplified,and the sequencing results confirmed the reliability of the NUMT analysis.One of them was polymorphic for the presence or absence of the NUMT insertion,and each genotype of NUMT loci showed a distinct regional distribution pattern.The information obtained in this study provides novel insights into the NUMT organization and features in bat genomes and establishes a basis for further studying of the evolution of bat species.展开更多
文摘核内线粒体DNA片段(nuclear mitochondrial DNA segments,Numts)给线粒体DNA的研究和应用带来了严重干扰,因而备受广大学者的关注。国内外学者在Numts的检测方面做了大量的研究。尤其是近年来,随着大量基因组数据的积累,相关研究不再局限于研究特定线粒体基因的核内同源片段,而是拓展到基因组水平上比较不同物种的Numts含量和分布,物种内部Numts的多态性也日益被研究者重视。该文从Numts的形成机制、检测方法、数量和分布对线粒体DNA研究的干扰及排除方法等方面进行了总结与归纳,也对Numts的研究意义与未来的发展趋势进行了简要分析。
基金the National Natural Science Foundation of China (No. 30470936)
文摘Mitochondrial DNA sequences transferred to the nucleus give rise to the so-called nuclear mitochondrial DNA （numt）. In the GenBank database, 244 numts have been found in six orders of birds （Anseriformes, Columbiformes, Falconiformes, Charadriiformes, Galliformes and Passeriformes）. Sequences alignment （NCBI-BLASTN） was carded out with mitochondrial and corresponding nuclear genome sequences in nine vertebrate species. The sequences with high homology were considered as numts. The number of numts ranged from 15 in chicken to 159 in chimpanzee. The sequences of numts in macaque, chimpanzee, and human spanned 100% of the entire mammalian mitochondrial genome. The reconstructed frequency of the mitochondrial gene transferred to the nucleus demonstrated that the rRNA genes had high frequencies than other mitochondrial genes. Using the RepeatMasker program, the transposable elements were detected in the flanking regions of each numt. The results showed that less than 5% of the flanking sequences were made up of repetitive elements in chicken. The GC content of 5＇- and 3＇-flanking regions of numts in nine species was less than 44%. The analysis of the flanking sequences provided a valuable understanding for future study on mechanism of mitochondrial gene transfer to the nucleus and the site of numt integration.
文摘In the human the peptide Humanin is produced from the small Humanin gene which is embedded as a gene-within-a-gene in the 16S ribosomal molecule of the mitochondrial DNA （mtDNA）. The peptide itself appears to be significant in the prevention of cell death in many tissues and improve cognition in animal models. By using simple data mining techniques, it is possible to show that 99.4% of the human Humanin sequences in the GenBank database are unaffected by mutations. However, in other vertebrates, pseudogenization of the Humanin gene is a common feature; occurring apparently randomly in some species and not others. The persistence, or loss, of a functional Humanin gene may be an important factor in laboratory animals, especially if they are being used as animal models in studies of Alzheimer＇s disease （AD）. The exact reason why Humanin underwent pseudogenization in some vertebrate species during their evolution remains to be determined. This study was originally planned to review the available information about Humanin and it was a surprise to be able to show that pseudogenization has occurred in a gene in the mtDNA and is not restricted solely to chromosomal genes.
文摘The discovery of Paranthropus deyiremeda in 3.3 - 3.5 million-year-old fossil sites in Afar, together with 30% of the gorilla genome showing lineage sorting between humans and chimpanzees, and a NUMT (“nuclear mitochondrial DNA segment”) on chromosome 5 that is shared by both gorillas, humans and chimpanzees, and shown to have diverged at the time of the Pan-Homo split rather than the Gorilla/Pan-Homo split, provides conclusive evidence that introgression from the gorilla lineage caused the Pan-Homo split, and the speciation of both the Australopithecus lineage and the Paranthropus lineage.
基金financial y supported by Shenzhen Polytechnic University Research Project(Grant No.6024330001K)to Ling Tianthe National Natural Science Foundation of China(No.32372662)+2 种基金the Science Fund Program for Distinguished Young Scholars of the National Natural Science Foundation of China(Overseas)to Yongfeng Zhouthe National Key Research and Development Program of China(No.2023YFD2200700)supported by the project of State Key Laboratory of Tropical Crop Breeding(No.NKLTCB-RC202501,No.NKLTCBCXTD40,No.SKLTCBBSH202501)。
文摘DNAs from the cytoplasmic genomes often communicate with the nuclear genome during regulation,development,and evolution.However,the dynamics of cytonuclear interaction during crop domestication have still been rarely investigated.Here,we examine cytonuclear interactions during grapevine domestication using pan-mitogenome,pan-plastome,and haplotype-resolved nuclear genomes,all assembled from long-read sequences across 33 wild and domesticated grapevine accessions.Structural variation shaped the mitogenomic variation in gene contents,leading to duplications of three specific genes during grapevine domestication(one cox and two rpl genes).Extensive genomic signals of cytonuclear interactions were detected,including a total of212–431 nuclear–mitochondrial segments(NUMTs)and 95–205 nuclear–plastid segments(NUPTs).These results showed that NUMTs were under strong selection and were more abundant in cultivated grapes,whereas NUPTs dominated in wild grapes,indicating the evolutionary trajectories of cytonuclear interactions during grape domestication.Through Genome-Wide Association Study(GWAS),we identified 84 candidate genes associated with mitochondrial–nuclear genome interactions.Among these,the PFD1 gene acts as a signaling regulator,modulating specific signaling pathways regulated by the mitochondria.Interestingly,there are significantly more cytonuclear interaction genes near NUMTs than in other genomic regions,suggesting NUMTmediated interactions between the nuclear and mitochondrial genomes.Overall,our study provides evidence that NUMTs promote cytonuclear interaction during grapevine domestication,offering new insight into the impact of cytonuclear interactions on plant evolution,genetics,and breeding.
基金supported by the National Natural Science Foundation of China(82202078 and 82402203)the National Natural Science Foundation of Chongqing(CSTB2024NSCQLZX0005)+4 种基金the Major Project of the National Social Science Foundation of China(23&ZD203)the Open Project of the Key Laboratory of Forensic Genetics of the Ministry of Public Security(2022FGKFKT05)the Center for Archaeological Science of Sichuan University(23SASA01)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC20002)the Sichuan Science and Technology Program(2024NSFSC1518)。
文摘Human mitochondrial DNA(mt DNA)harbors essential mutations linked to aging,neurodegenerative diseases,and complex muscle disorders.Due to its uniparental and haploid inheritance,mt DNA captures matrilineal evolutionary trajectories,playing a crucial role in population and medical genetics.However,critical questions about the genomic diversity patterns,inheritance models,and evolutionary and medical functions of mt DNA remain unresolved or underexplored,particularly in the transition from traditional genotyping to largescale genomic analyses.This review summarizes recent advancements in data-driven genomic research and technological innovations that address these questions and clarify the biological impact of nuclear-mitochondrial segments(NUMTs)and mt DNA variants on human health,disease,and evolution.We propose a streamlined pipeline to comprehensively identify mt DNA and NUMT genomic diversity using advanced sequencing and computational technologies.Haplotype-resolved mt DNA sequencing and assembly can distinguish authentic mt DNA variants from NUMTs,reduce diagnostic inaccuracies,and provide clearer insights into heteroplasmy patterns and the authenticity of paternal inheritance.This review emphasizes the need for integrative multi-omics approaches and emerging long-read sequencing technologies to gain new insights into mutation mechanisms,the influence of heteroplasmy and paternal inheritance on mt DNA diversity and disease susceptibility,and the detailed functions of NUMTs.
基金supported by the National Natural Science Foundation of China(NSFC,No.U1704102 and No.31172056).
文摘The transfer of mitochondrial DNA to the nuclear genome gives rise to the nuclear DNA sequences of mitochon-drial origin(NUMTs),considered as a driving force in genome evolution.In this study,NUMTs in 23 bat genomes were investigated and compared systematically.The results showed that NUMTs existed in 22 genomes except for Noctilio leporinus,suggesting that mitochondrial fragment insertion in the nuclear genome was a common event in bat genomes.However,remarkable variations in NUMTs number,cumulative length,and proportion in the nu-clear genome were discovered across bat species.Further orthologous NUMT loci analysis of the Phyllostomidae family indicated that the NUMTs insertion events in bat genomes were homoplasy-free.The NUMTs were mainly inserted into the intergenic regions,particularly,co-localized with repetitive sequences(especially transposable el-ements).However,several NUMTs were inserted into genes,some of which were in the exon region of functional genes.One NUMT in the genome of Pteropus alecto surprisingly matched with cDNA of ATP8B3 that provided evidence of NUMTs with coding function.Phylogenic analysis on NUMTs originating from COXI and COXII loci highlighted 2 clusters of Yinpterochiroptera and Yangochiroptera for Chiroptera.Seven NUMTs from Rhinolophus ferrumequinum were amplified,and the sequencing results confirmed the reliability of the NUMT analysis.One of them was polymorphic for the presence or absence of the NUMT insertion,and each genotype of NUMT loci showed a distinct regional distribution pattern.The information obtained in this study provides novel insights into the NUMT organization and features in bat genomes and establishes a basis for further studying of the evolution of bat species.
