Interpreting NUMTs in forensic genetics: Seeing the forest for the trees

Abstract

Nuclear mitochondrial DNA (mtDNA) segments (NUMTs) were discovered shortly after sequencing the first human mitochondrial genome. They have earlier been considered to represent archaic elements of ancient insertion events, but modern sequencing technologies and growing databases of mtDNA and NUMT sequences confirm that they are abundant and some of them phylogenetically young. Here, we build upon mtDNA/NUMT review articles published in the mid 2010 s and focus on the distinction of NUMTs and other artefacts that can be observed in aligned sequence reads, such as mixtures (contamination), point heteroplasmy, sequencing error and cytosine deamination. We show practical examples of the effect of the mtDNA enrichment method on the representation of NUMTs in the mapped sequence data and discuss methods to bioinformatically filter NUMTs from mtDNA reads.

Keywords: Alignment; Bioinformatics; Forensic science; Mega-NUMTs; Mitochondrial DNA; MtDNA; NUMTs; Nuclear elements of mtDNA.