Abstract
Natural selection acts on the phenotype. Therefore, many mistakenly expect to observe its signatures only in the organism, while overlooking its impact on tissues, cells and subcellular compartments. This is particularly crucial in the case of the mitochondrial genome (mtDNA) which unlike the nucleus resides in multiple cellular copies, that may vary in sequence (heteroplasmy) and quantity among tissues. Since the mitochondrion is a hub for cellular metabolism, ATP production, and additional activities such as nucleotide biosynthesis and apoptosis, mitochondrial dysfunction leads to both tissue-specific and systemic disorders. Therefore, strong selective pressures act to maintain mitochondrial function via removal of deleterious mutations via purifying (negative) selection. In parallel, selection also acts on the mitochondrion to allow adaptation of cells and organisms to new environments and physiological conditions (positive selection). Nevertheless, unlike the nuclear genetic information, the mitochondrial genetic system incorporates closely interacting bi-genomic factors (i.e. encoded by the nuclear and mitochondrial genomes). This is further complicated by the order of magnitude higher mutation rate of the vertebrate mtDNA as compared to the nuclear genome. Such mutation rate difference generates a generous mtDNA mutational landscape for selection to act, but also requires tight mito-nuclear co-evolution to maintain mitochondrial activities. In this essay we will consider the unique mitochondrial signatures of natural selection at the organism, tissue, cell and single mitochondrion levels.
Highlights
All cells require ATP, as it is the most common cellular currency to do work
Such relocation of genetic material from the cytoplasm to the cell nucleus required adaptation of the former mitochondrial DNA-encoded genes to the nuclear genetic code and translation machinery, assimilation of the “new” genetic immigrants into the nuclear mode of gene regulation, which respond to chromatin remodeling, and required the acquisition of the protein properties that allow their re-import into the mitochondria to maintain their function
We previously found that such non-random mutational distribution throughout the mitochondrial DNA (mtDNA) occurred regardless of the heteroplasmy levels in two cell populations in identical twins, attesting for the impact of selection, at the level by which phenotypic consequences are expected for the organism, and at the cellular level (Avital et al, 2012)
Summary
All cells require ATP, as it is the most common cellular currency to do work. glycolysis provides the means to produce ATP when glucose is available, an order of magnitude and more efficient energy-production system emerged ∼2.5 billion years ago in eukaryotes through endosymbiosis between the ancestor of the mitochondria and the progenitor of eukaryotic cells (Sagan, 1967). We previously found that such non-random mutational distribution throughout the mtDNA occurred regardless of the heteroplasmy levels in two cell populations (blood and skeletal muscle) in identical twins, attesting for the impact of selection, at the level by which phenotypic consequences are expected for the organism, and at the cellular level (Avital et al, 2012).
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