Related Experiment Video
Updated: Aug 26, 2025
07:24
Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing
Published on: February 10, 2023
1.6K
Nuclear-embedded mitochondrial DNA sequences in 66,083 human genomes.
Wei Wei1,2, Katherine R Schon1,2,3, Greg Elgar4
1Department of Clinical Neuroscience, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Nature
|October 5, 2022
Summary
Mitochondrial DNA (mtDNA) continuously transfers to the cell nucleus, creating nuclear-mitochondrial segments (NUMTs). These NUMTs evolve differently from mtDNA, with new insertions occurring in the germline and cancers, shaping a dynamic human genome.
Area of Science:
- Genomics
- Molecular Biology
- Evolutionary Biology
Background:
- DNA transfer from mitochondria to the nucleus (forming nuclear-mitochondrial segments or NUMTs) is a remnant of endosymbiosis, with most NUMTs considered ancient.
- The landscape and dynamics of contemporary NUMT formation and evolution remain incompletely understood.
Purpose of the Study:
- To investigate the ongoing transfer of mitochondrial DNA (mtDNA) into the nuclear genome.
- To characterize the diversity, origin, and evolutionary dynamics of nuclear-mitochondrial segments (NUMTs) in the human population.
- To explore the role of NUMTs in human health, including cancer.
Main Methods:
- Analysis of whole-genome sequences from 66,083 individuals, including 12,509 cancer patients.
- Identification and characterization of nuclear-mitochondrial segments (NUMTs) and their mutational signatures.
- Investigation of NUMT insertion mechanisms and evolutionary pressures.
Main Results:
- Demonstrated ongoing transfer of mtDNA to the nucleus, contributing to a complex and dynamic NUMT landscape.
- Identified over 1,637 different NUMTs in >99% of individuals, with many arising after human-ape divergence.
- Observed de novo NUMT formation in the germline and cancers, with specific NUMTs potentially linked to tumor development.
Conclusions:
- The human nuclear genome harbors a dynamic and evolving collection of nuclear-mitochondrial segments (NUMTs) resulting from ongoing DNA transfer.
- NUMTs exhibit distinct evolutionary trajectories and mutational patterns compared to mitochondrial DNA, influenced by nuclear insertion mechanisms and selection.
- The prevalence and characteristics of NUMTs vary across individuals and cancer types, highlighting their potential role in genomic variation and disease.
Related Concept Videos
02:59Animal Mitochondrial Genetics
7.9K
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
7.9K
02:19Export of Mitochondrial and Chloroplast Genes
3.7K
A eukaryotic cell can have up to three different types of genetic systems: nuclear, mitochondrial, and chloroplast. During evolution, organelles have exported many genes to the nucleus; this transfer is still ongoing in some plant species. Approximately 18% of the Arabidopsis thaliana nuclear genome is thought to be derived from the chloroplast’s cyanobacterial ancestor, and around 75% of the yeast genome derived from the mitochondria’s bacterial ancestor. This export has occurred...
3.7K
01:29Non-nuclear Inheritance
21.6K
Most DNA resides in the nucleus of a cell. However, some organelles in the cell cytoplasm—such as chloroplasts and mitochondria—also have their own DNA. These organelles replicate their DNA independently of the nuclear DNA of the cell in which they reside. Non-nuclear inheritance describes the inheritance of genes from structures other than the nucleus.
21.6K
02:16Comparing Mitochondrial, Chloroplast, and Prokaryotic Genomes
12.7K
The present-day mitochondrial and chloroplast genomes have retained some of the characteristics of their ancestral prokaryotes and also have acquired new attributes during their evolution within eukaryotic cells. Like prokaryotic genomes, mitochondrial and chloroplast genomes neither bind with histone-like proteins nor show complex packaging into chromosome-like structures, as observed in eukaryotes. Unlike mitotic cell divisions observed in eukaryotic cells, mitochondria and chloroplasts...
12.7K
02:51Multi-species Conserved Sequences
4.0K
Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
4.0K
01:39Mitochondrial Protein Sorting
4.4K
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
4.4K