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The mitochondrial genome is a fundamental component of the eukaryotic domain of life, encoding for several important subunits of the Respiratory Chain, the main energy production system in cells. The processes by means of which mtDNA replicates, expresses itself and evolves have been explored over the years, although various aspects are still debated. In this review, we present several key points in modern research on the role of evolutionary forces in affecting mitochondrial genomes in Metazoa. In particular, we assemble the main data on their evolution, describing the contributions of mutational pressure, purifying and adaptive selection, and how they are related. We also provide data on the evolutionary fate of the mitochondrial synonymous variation, related to the non-synonymous variation, in comparison with the pattern detected in the nucleus. Elevated mutational pressure characterises the evolution of the mitochondrial synonymous variation, whereas purging selection, physiologically due to phenomena such as cell atresia and intracellular mtDNA selection, guarantees coding sequence functionality. This enables mitochondrial adaptive mutations to emerge and fix in the population, promoting mito-nuclear coevolution.

Evolutionary Patterns of the Mitochondrial Genome in Metazoa: Exploring the Role of Mutation and Selection in Mitochondrial Protein–Coding Genes