With sequencing now possible at high depth, we aim to examine mutation process directly, by examining the DNA of children and their parents. Mitochondrial DNA (mtDNA) provides a good starting point for such an investigation due to its compact size and high mutation rate. We have established an experimental and computational pipeline to study mtDNA mutations and heteroplasmy frequency shifts (Goto et al. 2011), therefore we are in great position to study the patterns and rates of mtDNA mutations at unprecedented detail. Our recent study suggested that mitochondrial DNA undergoes through a very small bottleneck during oogenesis and that the number of heteroplasmies in the offspring increases with maternal age at fertilization (Rebolledo Jaramillo, Su, et al. 2014). Collaborators: Anton Nekrutenko, Francesca Chiaromonte, Rasmus Nielsen (Figure : Afgan et al. 2011).
Mitochondrial mutation dynamics
Visiting Research Professor
Are egg cells in aging primates protected from mutations?
New mutations occur at increasing rates in the mitochondrial genomes of developing egg cells in aging rhesus monkeys, but the increases …
New mutations accumulate in reproductive cells of older mice
Older mice have more new mutations – changes in DNA sequence that occur in the individual rather than being inherited from a …
E Torres-González, KD Makova. Exploring the effects of mitonuclear interactions on mitochondrial DNA gene expression in humans. FRONT GENET, 2022.
B Arbeithuber, MA Cremona, J Hester, A Barrett, B Higgins, K Anthony, F Chiaromonte, FJ Diaz, KD Makova. Advanced age increases frequencies of de novo mitochondrial mutations in macaque oocytes and somatic tissues. P NATL ACAD SCI USA, 2022.
B Arbeithuber, J Hester, MA Cremona, N Stoler, A Zaidi, B Higgins, K Anthony, F Chiaromonte, FJ Diaz, KD Makova. Age-related accumulation of de novo mitochondrial mutations in mammalian oocytes and somatic tissues. PLOS BIOL, 2020.
N Stoler, B Arbeithuber, G Povysil, M Heinzl, R Salazar, KD Makova, I Tiemann-Boege, A Nekrutenko. Family reunion via error correction: an efficient analysis of duplex sequencing data. BMC BIOINFORMATICS, 2020.
A Barrett, B Arbeithuber, A Zaidi, P Wilton, IM Paul, R Nielsen, KD Makova. Pronounced somatic bottleneck in mitochondrial DNA of human hair. PHILOS T R SOC B, 2019.
A Zaidi, P Wilton, MS-W Su, IM Paul, B Arbeithuber, K Anthony, A Nekrutenko, R Nielsen, KD Makova. Bottleneck and selection in the germline and maternal age influence transmission of mitochondrial DNA in human pedigrees. P NATL ACAD SCI USA, 2019.
AA Zaidi, KD Makova. Investigating mitonuclear interactions in human admixed populations. NAT ECOL EVOL, 2019.
PR Wilton, AA Zaidi, KD Makova, R Nielsen. A Population Phylogenetic View of Mitochondrial Heteroplasmy. GENETICS, 2018.
MM Holland, KD Makova, JA McElhoe. Deep-Coverage MPS Analysis of Heteroplasmic Variants within the mtGenome Allows for Frequent Differentiation of Maternal Relatives. GENES-BASEL, 2018.
RJ Baker, B Dickins, JK Wickliffe, FAA Khan, S Gaschak, KD Makova, CD Phillips. Elevated mitochondrial genome variation after 50 generations of radiation exposure in a wild rodent. EVOL APPL, 2017.
B Arbeithuber, KD Makova, I Tiemann-Boege. Artifactual mutations resulting from DNA lesions limit detection levels in ultrasensitive sequencing applications. DNA RES, 2016.
N Stoler, B Arbeithuber, WM Guiblet, KD Makova, A Nekrutenko. Streamlined analysis of duplex sequencing data with Du Novo. GENOME BIOL, 2016.
JA McElhoe, MM Holland, KD Makova, MS-W Su, IM Paul, CH Baker, SA Faith, B Young. Development and assessment of an optimized next-generation DNA sequencing approach for the mtgenome using the Illumina MiSeq. FORENSIC SCI INT-GEN, 2014.
B Rebolledo-Jaramillo, MS-W Su, N Stoler, JA McElhoe, B Dickins, D Blankenberg, TS Korneliussen, F Chiaromonte, R Nielsen, MM Holland, IM Paul, A Nekrutenko, KD Makova. Maternal age effect and severe germ-line bottleneck in the inheritance of human mitochondrial DNA. P NATL ACAD SCI USA, 2014.
B Dickins, B Rebolledo-Jaramillo, MS-W Su, IM Paul, D Blankenberg, N Stoler, KD Makova, A Nekrutenko. Controlling for contamination in re-sequencing studies with a reproducible web-based phylogenetic approach. BIOTECHNIQUES, 2014.
CC Steiner, KD Makova, OA Ryder. Mitochondrial Genome: Clues about the Evolution of Extant Equids and Genomic Diversity of Horse Breeds. EQUINE GENOMICS, 2013.
E Afgan, D Baker, N Coraor, H Goto, IM Paul, KD Makova, A Nekrutenko, J Taylor. Harnessing cloud computing with Galaxy Cloud. NAT BIOTECHNOL, 2011.
H Goto, B Dickins, E Afgan, IM Paul, J Taylor, KD Makova, A Nekrutenko. Dynamics of mitochondrial heteroplasmy in three families investigated via a repeatable re-sequencing study. GENOME BIOL, 2011.
H Goto, OA Ryder, AR Fisher, B Schultz, SL Kosakovsky Pond, A Nekrutenko, KD Makova. A Massively Parallel Sequencing Approach Uncovers Ancient Origins and High Genetic Variability of Endangered Przewalski's Horses. GENOME BIOL EVOL, 2011.