The genomic landscape of polymorphic human nuclear mitochondrial insertions

Dayama, Gargi; Emery, Sarah B.; Kidd, Jeffrey M.; Mills, Ryan E.

doi:10.1093/nar/gku1038

Cited by 175 publications

(203 citation statements)

References 60 publications

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“…They found correlations between the genetic diversity of the NUMTs and their geographical distribution. A more recent large-scale analysis of 23 polymorphic NUMTs was performed by Dayama et al, wherein they established that most of the polymorphic NUMTs were integrated within the past million years [22]. More than 50% of those NUMTs were present in low frequencies (>0.1%), indicating that their insertions were even more recent.…”

Section: Numtogenesis In Health Diversity Disease and Cancermentioning

confidence: 99%

“…Yao et al illustrated this concern as the contribution of the NUMTs can often be ignored when some mtDNA mutations are encountered in cancer [106]. Second, the effects of NUMTs and NUMT polymorphisms are often downplayed in studies of mitochondrial heteroplasmy [22, 107], defined as cellular differences in individual mitochondrial genomes due to high rates of mutations [63]. Since mitochondrial heteroplasmy has been implicated in aging and cancer [26, 81], it is the effect of NUMTs is appropriate to minimized on these processes.…”

Section: Numtogenesis In Health Diversity Disease and Cancermentioning

confidence: 99%

“…Since mitochondrial heteroplasmy has been implicated in aging and cancer [26, 81], it is the effect of NUMTs is appropriate to minimized on these processes. Dayama et al identified several sites in the mitochondrial genome that have hitherto been mistaken as mutated when the mutations were actually present in NUMTs [22]. In addition, there are reports of different frequencies of NUMTs.…”

Section: Numtogenesis In Health Diversity Disease and Cancermentioning

confidence: 99%

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Numtogenesis as a mechanism for development of cancer

Singh¹,

Choudhury

Tiwari

2017

Seminars in Cancer Biology

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Transfer of genetic material from cytoplasmic organelles to the nucleus, an ongoing process, has implications in evolution, aging, and human pathologies such as cancer. The transferred mitochondrial DNA (mtDNA) fragments in the nuclear genome are called nuclear mtDNA or NUMTs. We have named the process numtogenesis, defining the term as the transfer of mtDNA into the nuclear genome, or, less specifically, the transfer of mitochondria or mitochondrial components into the nucleus. There is increasing evidence of the involvement of NUMTs in human biology and pathology. Although information pertaining to NUMTs and numtogenesis is sparse, the role of this aspect of mitochondrial biology to human cancers is apparent. In this review, we present available knowledge about the origin and mechanisms of numtogenesis, with special emphasis on the role of NUMTs in human malignancies. We describe studies undertaken in our laboratory and in others and discuss the influence of NUMTs in tumor initiation and progression and in survival of cancer patients. We describe suppressors of numtogenesis and evolutionary conserved mechanisms underlying numtogenesis in cancer. An understanding the emerging field of numtogenesis should allow comprehension of this process in various malignancies and other diseases and, more generally, in human health.

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Section: Numtogenesis In Health Diversity Disease and Cancermentioning

confidence: 99%

Section: Numtogenesis In Health Diversity Disease and Cancermentioning

confidence: 99%

Section: Numtogenesis In Health Diversity Disease and Cancermentioning

confidence: 99%

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Numtogenesis as a mechanism for development of cancer

Singh¹,

Choudhury

Tiwari

2017

Seminars in Cancer Biology

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“…NUMT insertion is a genetically frequent event that is estimated to occur at a rate of ~5 × 10 −6 per germ cell per generation in humans [140]. Although NUMTs have been reported in at least 85 sequenced eukaryotic genomes [139, 141, 142], the exact mechanism(s) of NUMT accumulation in the nucleus is not yet known.…”

Section: Mitochondria In Intracellular Information Transfermentioning

confidence: 99%

Defining the momiome: Promiscuous information transfer by mobile mitochondria and the mitochondrial genome

Singh

Modica-Napolitano

Singh

2017

Seminars in Cancer Biology

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Mitochondria are complex intracellular organelles that have long been identified as the powerhouses of eukaryotic cells because of the central role they play in oxidative metabolism. A resurgence of interest in the study of mitochondria during the past decade has revealed that mitochondria also play key roles in cell signaling, proliferation, cell metabolism and cell death, and that genetic and/or metabolic alterations in mitochondria contribute to a number of diseases, including cancer. Mitochondria have been identified as signaling organelles, capable of mediating bidirectional intracellular information transfer: anterograde (from nucleus to mitochondria) and retrograde (from mitochondria to nucleus). More recently, evidence is now building that the role of mitochondria extends to intercellular communication as well, and that the mitochondrial genome (mtDNA) and even whole mitochondria are indeed mobile and can mediate information transfer between cells. We define this promiscuous information transfer function of mitochondria and mtDNA as “momiome” to include all mobile functions of mitochondria and the mitochondrial genome. Herein we review the “momiome” and explore its role in cancer development, progression, and treatment.

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“…Although NUMTs are transcriptionally inactive, recent findings have suggested that in mammals integration of NUMTs is non-random [26,27]. The human genome contains NUMT, with mtDNA identities ranging from 64 to 100% [28,29]. We describe this phenomenon of insertion of mtDNA fragments into nuclear genome as ‘ numtogenesis ’.…”

Section: Introductionmentioning

confidence: 99%

Single molecule mtDNA fiber FISH for analyzing numtogenesis

Koo

Singh

Jiang

et al. 2018

Analytical Biochemistry

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Somatic human cells contain thousands of copies of mitochondrial DNA (mtDNA). In eukaryotes, natural transfer of mtDNA into the nucleus generates nuclear mitochondrial DNA (NUMT) copies. We name this phenomenon as “numtogenesis”. Numtogenesis is a well-established evolutionary process reported in various sequenced eukaryotic genomes. We have established a molecular tool to rapidly detect and analyze NUMT insertions in whole genomes. To date, NUMT analyses depend on deep genome sequencing combined with comprehensive computational analyses of the whole genome. This is time consuming, cumbersome and cost prohibitive. Further, most laboratories cannot accomplish such analyses due to limited skills. We report the development of single-molecule mtFIBER FISH (fluorescence in situ hybridization) to study numtogenesis. The development of mtFIBER FISH should aid in establishing a role for numtogenesis in cancers and other human diseases. This novel technique should help distinguish and monitor cancer stages and progression, aid in elucidation of basic mechanisms underlying tumorigenesis and facilitate analyses of processes related to early detection of cancer, screening and/or cancer risk assessment.

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The genomic landscape of polymorphic human nuclear mitochondrial insertions

Cited by 175 publications

References 60 publications

Numtogenesis as a mechanism for development of cancer

Numtogenesis as a mechanism for development of cancer

Defining the momiome: Promiscuous information transfer by mobile mitochondria and the mitochondrial genome

Single molecule mtDNA fiber FISH for analyzing numtogenesis

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