Mitonuclear interactions: evolutionary consequences over multiple biological scales

Abstract

Fundamental biological processes hinge on coordinated interactions between genes spanning two obligate genomes—mitochondrial and nuclear. These interactions are key to complex life, and allelic variation that accumulates and persists at the loci embroiled in such intergenomic interactions should therefore be subjected to intense selection to maintain integrity of the mitochondrial electron transport system. Here, we compile evidence that suggests that mitochondrial–nuclear (mitonuclear) allelic interactions are evolutionarily significant modulators of the expression of key health-related and life-history phenotypes, across several biological scales—within species (intra- and interpopulational) and between species. We then introduce a new frontier for the study of mitonuclear interactions—those that occur within individuals, and are fuelled by the mtDNA heteroplasmy and the existence of nuclear-encoded mitochondrial gene duplicates and isoforms. Empirical evidence supports the idea of high-resolution tissue- and environment-specific modulation of intraindividual mitonuclear interactions. Predicting the penetrance, severity and expression patterns of mtDNA-induced mitochondrial diseases remains a conundrum. We contend that a deeper understanding of the dynamics and ramifications of mitonuclear interactions, across all biological levels, will provide key insights that tangibly advance our understanding, not only of core evolutionary processes, but also of the complex genetics underlying human mitochondrial disease.

Maternal inheritance of mitochondria: implications for male fertility?

“…We believe the coming years will provide crucial resolution of these questions, inspired by emerging research that suggests a role for the Mother's Curse hypothesis in human reproductive biology (Dowling 2014, Milot et al 2017.…”

“…These studies have routinely linked the genetic variation that delineates naturally occurring 'mtDNA haplotypes' to modifications in a range of phenotypes related to health, such as metabolism, growth and longevity, in both invertebrate (Rand 2001, Meikeljohn et al 2007, Camus et al 2012, Yee et al 2013) and vertebrate metazoans (Fontanillas et al 2005, Smith et al 2010, Boratyński et al 2016. Many of these papers have been reviewed elsewhere (Ballard & Kreitman 1995, Blier 2001, Ballard & Whitlock 2004, Ballard & Rand 2005, Dowling et al 2008, Ballard & Pichaud 2014, Dobler et al 2014, Dowling 2014 and will not be discussed here. Coupled with these findings, it has become increasingly clear that diseasecausing mtDNA mutations might commonly exist at appreciable frequencies within human populations (Chinnery et al 2000, Taylor & Turnbull 2005, Reeve et al 2008, with around one in 200 people estimated to carry a pathogenic mtDNA mutation (Elliott et al 2008), and around one in 5000 ultimately expressing a mitochondrial disease phenotype at some stage of their lives (Thorburn 2004).…”

“…Furthermore, different mtDNA variants have recently been implicated in the penetrance or severity of a range of late-onset human diseases that were previously thought to be unrelated to mitochondrial function, from schizophrenia, to multiple sclerosis and Parkinson's disease (Hudson et al 2014). Thus, it is becoming apparent that the genetic variation that accumulates within the mtDNA sequences of natural populations of metazoans does play an important role in determining health outcomes, by contributing to metabolic health, development trajectories, lifespan and the risk of disease progression (Wallace 2005, Dowling et al 2008, Reinhardt et al 2013, Dowling 2014.…”

“…The evolutionary implication is that the production of ATP, the key energy currency on which the integrity of eukaryotic life relies, depends on a coordinated set of interactions between genes that reside across two obligate genomes (Fig. 1) -mitochondrial and nuclear (Rand et al 2004, Wolff et al 2014). …”

Reproductive activity triggers accelerated male mortality and decreases lifespan: genetic and gene expression determinants in Drosophila

“…Interestingly, mitochondrial DNA variation in Drosophila preferentially affects genes that are exclusively expressed in the testis (Innocenti et al, 2011). When probed in engineered genotypes that differ only in their mitochondrial DNA haplotype, males display significantly higher genetic variance for longevity than females (Camus et al, 2012;Dowling, 2014;Wolff et al, 2014). Variation in Y-linked heterochromatin is also known to modulate the expression of genes exclusively transcribed in reproductive tissues as well as genes associated with mitochondrial function in Drosophila (Lemos et al, 2008(Lemos et al, , 2010.…”