Mitochondrial DNA Purifying Selection in Mammals and Invertebrates

• Published in: Journal of molecular biology 2018-12, Vol.430 (24), p.4834-4848
• Main Authors: Palozzi, Jonathan M., Jeedigunta, Swathi P., Hurd, Thomas R.
• Format: Article
• Language: English
• Subjects: germline; mitochondria; mitochondrial DNA; purifying selection
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2018.10.019

Numerous mitochondrial quality control mechanisms exist within cells, but none have been shown to effectively assess and control the quality of mitochondrial DNA (mtDNA). One reason such mechanisms have yet to be elucidated is that they do not appear to be particularly active in most somatic cells, where many studies are conducted. The female germline, the cell lineage that gives rise to eggs, appears to be an exception. In the germline, strong purifying selection pathways act to eliminate deleterious mtDNA. These pathways have apparently evolved to prevent pathogenic mtDNA mutations from accumulating over successive generations and causing a decline of species via Muller's ratchet. Despite their fundamental biological importance, the mechanisms underlying purifying selection remain poorly understood, with no genes involved in this process yet identified. In this review, we discuss recent studies exploring mechanisms of germline mtDNA purifying selection in both mammalian and invertebrate systems. We also discuss the challenges to future major advances. Understanding the molecular basis of purifying selection is not only a fundamental outstanding question in biology, but may also pave the way to controlling selection in somatic tissues, potentially leading to treatments for people suffering from mitochondrial diseases. [Display omitted] •Pathways to eliminate deleterious mitochondrial DNA are active in the female germline but remain poorly understood.•Advances in mammalian and Drosophila systems have begun to illuminate wherein germline development purifying selection against deleterious mitochondrial DNA occurs.•The molecular mechanism of purifying selection remains unknown, with no genes involved in the process yet identified.•Tools to visualize purifying selection as it occurs and models to study selection in vitro are much needed.