.2016 Dec 15;25(24):5332-5338.

doi: 10.1093/hmg/ddw347.

Evidence for mitochondrial genetic control of autosomal gene expression

Irfahan Kassam¹, Tuan Qi¹, Luke Lloyd-Jones¹, Alexander Holloway¹, Marc Jan Bonder², Anjali K Henders¹, Nicholas G Martin³, Joseph E Powell^{1 4}, Lude Franke², Grant W Montgomery³, Peter M Visscher^{1 5}, Allan F McRae¹

Affiliations

¹ Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
² Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
³ QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
⁴ Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
⁵ University of Queensland Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, QLD, Australia.

PMID:27798101
PMCID: PMC6078603
DOI: 10.1093/hmg/ddw347

Evidence for mitochondrial genetic control of autosomal gene expression

Irfahan Kassam et al. Hum Mol Genet.2016.

.2016 Dec 15;25(24):5332-5338.

doi: 10.1093/hmg/ddw347.

Authors

Affiliations

¹ Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
² Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
³ QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
⁴ Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
⁵ University of Queensland Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, QLD, Australia.

PMID:27798101
PMCID: PMC6078603
DOI: 10.1093/hmg/ddw347

Abstract

The mitochondrial and nuclear genomes coordinate and co-evolve in eukaryotes in order to adapt to environmental changes. Variation in the mitochondrial genome is capable of affecting expression of genes on the nuclear genome. Sex-specific mitochondrial genetic control of gene expression has been demonstrated in Drosophila melanogaster, where males were found to drive most of the total variation in gene expression. This has potential implications for male-related health and disease resulting from variation in mtDNA solely inherited from the mother. We used a family-based study comprised of 47,323 gene expression probes and 78 mitochondrial SNPs (mtSNPs) from n = 846 individuals to examine the extent of mitochondrial genetic control of gene expression in humans. This identified 15 significant probe-mtSNP associations (P<10-8) corresponding to 5 unique genes on the mitochondrial and nuclear genomes, with three of these genes corresponding to mitochondrial genetic control of gene expression in the nuclear genome. The associated mtSNPs for three genes (one cis and two trans associations) were replicated (P < 0.05) in an independent dataset of n = 452 unrelated individuals. There was no evidence for sexual dimorphic gene expression in any of these five probes. Sex-specific effects were examined by applying our analysis to males and females separately and testing for differences in effect size. The MEST gene was identified as having the most significantly different effect sizes across the sexes (P≈10-7). MEST was similarly expressed in males and females with the G allele; however, males with the C allele are highly expressed for MEST, while females show no expression of the gene. This study provides evidence for the mitochondrial genetic control of expression of several genes in humans, with little evidence found for sex-specific effects.

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Figures

**Figure 1**
Quantile-quantile plot for expected versus observed p-values of 3,691,194 probe-mtSNP associations. A strong deviation from the expected is observed for large $- l o g_{10} (P)$ .

**Figure 2**
Boxplot of normalised expression intensity levels for each of the top five probes versus the alleles of the top associated mtSNP.

**Figure 3**
Intersections between the sets of significant probe-mtSNP associations.

**Figure 4**
A boxplot of the raw gene expression intensities ofMEST versus the alleles of the associated mtSNP across the sexes.

See this image and copyright information in PMC

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References

1. Mishra P., Chan D.C. (2014) Mitochondrial dynamics and inheritance during cell division, development and disease. Nat. Rev. Mol. Cell Biol., 15, 634–646. - PMC - PubMed
1. Greiner S., Bock R. (2013) Tuning a ménage à trois: co-evolution and co-adaptation of nuclear and organellar genomes in plants. Bioessays, 35, 354–365. - PubMed
1. Woodson J.D., Chory J. (2008) Coordination of gene expression between organellar and nuclear genomes. Nat. Rev. Genet., 9, 383–395. - PMC - PubMed
1. Hwang S., Kwak S.H., Bhak J., Kang H.S., Lee Y.R., Koo B.K., Park K.S., Lee H.K., Cho Y.M. (2011) Gene expression pattern in transmitochondrial cytoplasmic hybrid cells harboring type 2 diabetes-associated mitochondrial DNA haplogroups. PLoS One, 6, e22116.. - PMC - PubMed
1. Innocenti P., Morrow E.H., Dowling D.K. (2011) Experimental evidence supports a sex-specific selective sieve in mitochondrial genome evolution. Science, 332, 845–848. - PubMed

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Evidence for mitochondrial genetic control of autosomal gene expression

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Evidence for mitochondrial genetic control of autosomal gene expression

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