Characterization Of Mitochondrial Genome Indels In Individuals Classified By High And Low Vo 2max Trainability

PURPOSE: Recently published work by our group identified mitochondrial DNA (mtDNA) variants and heteroplasmy that differ between individuals categorized by high and low aerobic capacity (VO2max) trainability, part of the HERITAGE Family Study Cohort. Our purpose in this investigation was to assess insertions and deletions (indels) in mitochondrial genomes in high (HR) and low responders (LR). METHODS: DNA was isolated from whole blood in HERITAGE Family Study healthy subjects (subjects classified by change in VO2max: HR: n = 15; LR: n = 15). mtDNA was amplified by long-range polymerase chain reaction, then tagged with Nextera libraries, and sequenced on a Miseq instrument. An indel was defined as an insertion or deletion with a frequency of at least 1% at a specific location. For this study, we compared indel sites and the frequency they occurred between HR and LRs. RESULTS: Among subjects, we identified 11 total sites where an indel occurred in at least one individual: mtHVR2 (C285CA: LR = 1 individual; HR = 0 individuals), mtHVR2 (A302AC: LR = 1 individual; HR = 0 individuals), mtHVR3 (G513GCA: LR = 1 individual; HR = 1 individual), mtHVR3 (GCA513G: LR = 3 individuals; HR = 1 individual), mtHVR3 (A567AC: LR = 0 individuals; HR = 1 individual), mtND4 (GA11031G: LR = 0 individuals; HR = 1 individual), mtND5 (CA12417C: LR = 11 individuals; HR = 8 individuals), mtHVR1(CA16179C: LR = 0 individuals; HR = 2 individuals), mtHVR1 (A16182AC: LR = 0 individuals; HR = 2 individuals), mtHVR1 (CT16188C: LR = 0 individuals; HR = 3 individuals), mtHVR1(C16192CT: LR = 0 individual; HR = 1 individual). The average total frequency across the indels in LR was 41.32 % (± 43.55 %) and 31.59 % (± 33.29 %) in HRs. We identified three sites with indels that were present in HR but not LR: mtHVR1 (CA16179C; 21.5% ± 0.71% mean indel frequency), mtHVR1 (A16182AC; 13.4% ± 0.57% mean indel frequency), and mtHVR1 (CT16188C; 17.4% ± 21.45% mean indel frequency). CONCLUSIONS: We found three sites with indels in the HVR1 region of the mitochondrial genome in HR but not LR. While our sample size is small, our findings highlight an area of the mitochondrial genome that is responsible for mtDNA replication that presents indels in individuals classified by low trainability. Our on-going work is to increase the sample size and assess indel implications on VO2max trainability.