bims-humivi 2026-10-11 papers

Issue of 2026–10–11
three papers selected by
Mariangela Santorsola, Università di Pavia

Nat Rev Genet. 2026 Oct 05.

Inheritance and selection of the mitochondrial genome.

Qin Xie, Harry E Walker, Michal Minczuk, Marcos R Chiaratti, Patrick F Chinnery.

The functioning mitochondrial genome is essential for cellular energy production. Being strictly maternally inherited and possessing limited DNA repair capacity, mitochondrial DNA (mtDNA) replication errors tend to accumulate over time. If left unchecked, these errors can accumulate through the female germline over successive generations, potentially leading to species extinction. However, this outcome is not observed in most species, including humans, which implies the existence of mechanisms that counteract the progressive accumulation of deleterious mtDNA mutations. Recent technological advances are building a deeper understanding of the processes that preserve mtDNA integrity, including the molecular and cellular basis and timing of purifying selection. This new knowledge helps to explain how mtDNA can change rapidly over just a few generations, whilst remaining compatible with the independently inherited, evolving nuclear genome.

DOI: https://doi.org/10.1038/s41576-026-01019-0

Neurol Neurochir Pol. 2026 Oct 05.

Genetic insights into multiple sclerosis: exploring mitochondrial DNA and nuclear POLG gene variation in a Polish single-center RRMS cohort.

Agnieszka Piotrowska-Nowak, Biruta Kierdaszuk, Ada M Dziedzicka, Magdalena Kaliszewska, Aleksandra Podlecka-Piętowska, Katarzyna Tońska.

AIM OF THE STUDY: To evaluate the contribution of mitochondrial DNA (mtDNA) variation and four POLG mutations to disease susceptibility and course in Polish patients with relapsing-remitting multiple sclerosis (RRMS).
CLINICAL RATIONALE FOR THE STUDY: Mitochondrial dysfunction is increasingly implicated in the pathogenesis of multiple sclerosis (MS), yet its precise role remains unclear. Determining the impact of mtDNA variation and POLG mutations may improve understanding of factors influencing disease onset and progression.
MATERIAL AND METHODS: Whole mtDNA was sequenced in 100 RRMS patients using next-generation sequencing and compared with previously generated mtDNA data from 212 Polish individuals without MS. The presence of pathogenic variants, distribution of haplogroups, rare variants, and heteroplasmy were assessed. Absolute mtDNA copy number was measured by real-time PCR. Additionally, RRMS patients were screened for four common POLG mutations (p.Gly268Ala, p.Ala467Thr, p.Pro587Leu, and p.Trp748Ser).
RESULTS: No pathogenic mtDNA variants or any of the four screened POLG variants were detected. No significant associations were found between major mtDNA haplogroups, copy number, heteroplasmy, or rare variants and MS risk or progression. Exploratory analyses identified nominal associations between several mtDNA variants and relapse occurrence, disability level, age at symptom onset, and sex in the RRMS cohort.
CONCLUSIONS AND CLINICAL IMPLICATIONS: Pathogenic mtDNA variants, major haplogroups, mtDNA copy number, rare variant burden, and the four screened POLG variants do not appear to play a major role in RRMS susceptibility or clinical course in the analyzed cohort. Several associations involving individual mtDNA variants were identified, but these findings are exploratory and require independent replication in larger cohorts before their biological or clinical relevance can be established.

Keywords: EDSS; POLG gene; genetic variation; mitochondrial DNA; mitochondrial disorders; multiple sclerosis; relapses

DOI: https://doi.org/10.5603/pjnns.113007

Mol Ecol Resour. 2026 Oct;26(7): e70211

MitoNumt: A Workflow for Recovering Mitochondrial Genomes From Long-Read Data and Detecting NUMT Contamination in Mitochondrial Genome Assemblies.

Ruidong Cao, Tong Xin, Yubo Hao, Yibo Hu.

Nuclear mitochondrial DNA segments (NUMTs) are genomic DNA fragments that originate from historical insertions of mitochondrial DNA sequences into the nuclear genome. During mitochondrial genome (mtgenome) assembly from short-read genome sequencing data, NUMT fragments may be misidentified and incorporated into mtgenome assemblies, leading to NUMT contamination. Although some assembly programs include steps to filter NUMTs, these approaches are not always effective. Here, we present MitoNumt, a multifunctional workflow. Using this pipeline, we recovered mtgenomes, complete NUMT (coexistence with the mtgenomes), and incomplete NUMT fragments from PacBio HiFi long-read sequencing data for five species of the genus Panthera and Puma concolor. We then used these sequences to check mtgenomes available in the NCBI database. NUMT contamination was detected in mtgenomes from all Panthera species examined, with 23 contaminated mtgenomes identified and contamination lengths ranging from 3 to 416 bp. In addition, phylogenetic trees reconstructed from NUMT fragments of at least 5000 bp consistently recovered a topology congruent with the currently accepted Panthera phylogeny. Overall, this workflow enables the identification of HiFi-supported mtgenomes and complete NUMTs, and the detection of NUMT contamination in assembled mtgenomes, thereby improving the reliability of mtgenome-based evolutionary and genetic studies.

Keywords: Panthera ; NUMT; mitochondrial genome; phylogenetic analyses

DOI: https://doi.org/10.1111/1755-0998.70211