Related Experiment Video
Updated: Sep 8, 2025
07:24
Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing
Published on: February 10, 2023
1.6K
Cell type-specific purifying selection of synonymous mitochondrial DNA variation.
Caleb A Lareau1,2, Patrick Maschmeyer3,4, Yajie Yin2
1Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
Summary
Synonymous mitochondrial DNA variants can impact cell fitness. A specific variant in MT-CO1 showed selection against it in CD8+ T cells due to translation stalling, affecting mitochondrial function.
Area of Science:
- Genetics
- Cell Biology
- Immunology
Background:
- Somatic variants are known drivers of cancer, but their role in nonmalignant cells is less understood.
- Mitochondrial DNA (mtDNA) variants can affect cellular energy production and function.
Purpose of the Study:
- To investigate the impact of a mosaic synonymous mtDNA variant on cellular fitness in immune cells.
- To understand the mechanism of selection against this variant in specific T cell subsets.
Main Methods:
- Single-cell multiomics analysis
- Mitochondrial ribosome profiling
- Functional assays
Main Results:
- A synonymous variant (m.7076A > G) in MT-CO1 was identified in 47% of immune cells from a healthy donor.
- Strong lineage-specific selection against the m.7076G allele was observed in CD8+ effector memory T cells.
- The variant caused translation stalling due to altered codon pairing, impacting mitochondrial physiology.
Conclusions:
- Synonymous mtDNA variants can exert selective pressure in a cell type-specific manner.
- The metabolic demands of effector T cells amplify the impact of MT-CO1 variants.
- Codon syntax alterations by synonymous variants can influence mitochondrial function in nonmalignant contexts.
Related Concept Videos
02:59Animal Mitochondrial Genetics
8.0K
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...
8.0K
02:19Export of Mitochondrial and Chloroplast Genes
3.8K
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...
3.8K
02:05Gene Evolution - Fast or Slow?
7.4K
The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...
In contrast, regions which code...
7.4K
02:16Comparing Mitochondrial, Chloroplast, and Prokaryotic Genomes
13.3K
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...
13.3K
02:51Multi-species Conserved Sequences
4.3K
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...
4.3K
02:54Evolutionary Relationships through Genome Comparisons
6.1K
Genome comparison is one of the excellent ways to interpret the evolutionary relationships between organisms. The basic principle of genome comparison is that if two species share a common feature, it is likely encoded by the DNA sequence conserved between both species. The advent of genome sequencing technologies in the late 20th century enabled scientists to understand the concept of conservation of domains between species and helped them to deduce evolutionary relationships across diverse...
6.1K