期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 430, 期 24, 页码 4834-4848出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2018.10.019
关键词
mitochondria; purifying selection; germline; mitochondrial DNA
资金
- Canadian Institutes of Health Research [FRN 159510]
- CFREF
- University of Toronto Open Fellowship
- Canada Graduate Scholarship-Master's
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. (C) 2018 Elsevier Ltd. All rights reserved.
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