Influence of environmental factors and genetic variation on mitochondrial DNA copy number

Authors: SANGLARD, LETICIA - University Of Nebraska; Kuehn, Larry; Snelling, Warren; SPANGLER, MATTHEW - University Of Nebraska

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/24/2022
Publication Date: 5/2/2022
Citation: Sanglard, L.P., Kuehn, L.A., Snelling, W.M., Spangler, M.L. 2022. Influence of environmental factors and genetic variation on mitochondrial DNA copy number. Journal of Animal Science. 100(5). Article skac059. https://doi.org/10.1093/jas/skac059.
DOI: https://doi.org/10.1093/jas/skac059

Interpretive Summary: Levels of mitochondrial DNA (mtDNA) correlate with mitochondrial. This study investigated the genetic and non-genetic factors influencing mitochondrial DNA content in a composite beef cattle population of 2,371 animals using low-pass sequencing. Blood, leucocyte, and semen samples were subjected to low-depth whole-genome sequencing that resulted in mtDNA and nuclear DNA coverages to estimate mtDNA content. Findings revealed that 11% to 31% of the variation in mtDNA content is under genetic control. Non-genetic effects of tissue type, age, and sex were significantly associated with mtDNA content. Semen samples had the lowest mtDNA content, followed by blood and leucocyte samples. Age had linear and quadratic effects on mtDNA content. Females had greater mtDNA content than males. Heterosis and breed composition were not significantly associated with mtDNA content. These results suggest that mtDNA content is heritable and would respond favorably to selection.

Technical Abstract: Mitochondrial DNA copy number (mtDNA CN) has been shown to be highly heritable and associated with traits of interest in humans. However, studies are lacking in the literature for livestock species such as beef cattle. In this study, 2,371 individuals from a crossbred beef population comprising the Germplasm Evaluation program from the U.S. Meat Animal Research Center had samples of blood, leucocyte, or semen collected for low-pass sequencing (LPS) that resulted in both nuclear DNA (nuDNA) and mitochondrial DNA (mtDNA) sequence reads. Mitochondrial DNA CN was estimated based on the ratio of mtDNA to nuDNA coverages. Genetic parameters for mtDNA CN were estimated from an animal model based on a genomic relationship matrix (~87K SNP from the nuDNA). Different models were used to test the effects of tissue, sex, age at sample collection, heterosis, and breed composition. Maternal effects, assessed by fitting a maternal additive component and by fitting eleven SNP on the mtDNA, were also obtained. As previously reported, mtDNA haplotypes were used to classify individuals into Taurine haplogroups (T1, T2, T3/T4, and T5). Estimates of heritability when fitting fixed effects in addition to the intercept were moderate, ranging from 0.11 to 0.31 depending on the model. From a model ignoring contemporary group, semen samples had the lowest mtDNA CN, as expected, followed by blood and leucocyte samples (P <= 0.001). The effect of sex and the linear and quadratic effects of age were significant (P <= 0.02) depending on the model. When significant, females had greater mtDNA CN than males. The effects of heterosis and maternal heterosis were not significant (P => 0.47). The estimates of maternal and mtDNA heritability were near zero (<=0.03). Most of the samples (98%) were classified as haplogroup T3. Variation was observed in the mtDNA within Taurine haplogroups, which enabled the identification of 24 haplotypes. These results suggest that mtDNA CN is under nuclear genetic control and would respond favorably to selection.