Characterization of nuclear mitochondrial insertions in canine genome assemblies

Abstract

Background: The presence of mitochondrial sequences in the nuclear genome (Numts) confounds analyses of mitochondrial sequence variation and is a potential source of false positives in disease studies. To improve the analysis of mitochondrial variation in canines, we completed a systematic assessment of Numt content across genome assemblies, canine populations and the carnivore lineage. Results: Centering our analysis on the UU_Cfam_GSD_1.0/canFam4/Mischka assembly, a commonly used reference in dog genetic variation studies, we find a total of 321 Numts, located throughout the nuclear genome and encompassing the entire sequence of the mitochondria. Comparison to 14 canine genome assemblies identified 63 Numts with presence-absence dimorphism among dogs, wolves, and a coyote. Further, a subset of Numts were maintained across carnivore evolutionary time (arctic fox, polar bear, cat), with 8 sequences likely more than 10 million years old, and shared with the domestic cat. On a population level, using structural variant data from the Dog10K Consortium for 1,879 dogs and wolves, we identified 11 Numts that are absent in at least one sample as well as 53 Numts that are absent from the Mischka assembly. Conclusions: We highlight scenarios where the presence of Numts is a potentially confounding factor and provide an annotation of these sequences in canine genome assemblies. This resource will aid the identification and interpretation of polymorphisms in both somatic and germline mitochondrial studies in canines.