Mitochondrial DNA Artefacts Distort Single-Cell Phylogeny

Artefacts present in single-cell mitochondrial DNA (mtDNA) analyses have been identified as a significant source of misinformation, leading to inaccurate reconstructions of phylogenetic trees. This discovery, detailed in a study published online in Nature on August 19, 2026, highlights a critical flaw in a commonly used methodology within evolutionary biology and genetics research. The research indicates that these artefacts can distort the perceived evolutionary relationships between organisms, potentially leading to erroneous conclusions about their ancestry and diversification.

Single-cell mtDNA sequencing is a powerful technique that allows researchers to examine the genetic material of individual cells. This approach is particularly valuable for studying cellular heterogeneity, developmental processes, and the evolution of complex organisms. However, the presence of artefacts—unintended or spurious results—can arise from various stages of the laboratory process, including DNA extraction, amplification, and sequencing. These artefacts can manifest as incorrect base calls, chimeric sequences, or variations that do not reflect the true genetic makeup of the cell.

The study specifically points to issues that arise during the amplification of mtDNA, a process often necessary to generate sufficient DNA for sequencing. If the amplification is not perfectly uniform or if it captures non-target DNA fragments, the resulting sequence data can be misleading. These errors can be amplified when analysing data from thousands or even millions of individual cells, making it difficult to distinguish genuine biological variation from technical noise. The implications are far-reaching, as phylogenetic trees are fundamental tools used to understand the evolutionary history of life on Earth, guiding research in fields such as paleontology, conservation biology, and medicine.

Researchers involved in the study emphasize the need for rigorous validation and the development of improved bioinformatic tools to detect and correct these mtDNA artefacts. Without such measures, the conclusions drawn from single-cell mtDNA phylogenies may be fundamentally flawed, impacting our understanding of evolutionary processes and the relationships between species. The publication in Nature, a leading scientific journal, underscores the significance of these findings and their potential to reshape current research practices in genomics and evolutionary studies. The doi for the article is 10.1038/s41586-026-10777-0.