Novel mtDNA-encoded proteins and mitochondrial sex determination in the Bivalvia (Mollusca)

双壳纲（软体动物）中新型 mtDNA 编码蛋白和线粒体性别决定

• 批准号: 435656-2013
• 负责人: Breton, Sophie
• 金额: $ 2.99万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629102
• 关键词: Novel; mtDNA; encoded; proteins; mitochondrial

Mitochondria (mt) are known as the "powerhouses of the cell" because they are responsible for most of the energy production in animal cells. They contain their own DNA (mtDNA), which codes for 13 proteins that are involved in energy production. Mutations in mtDNA are responsible for several human diseases including diabetes and cancer. The inheritance of mtDNA in animals has long been believed to be strictly maternal until the discovery of a radically different Doubly Uniparental Inheritance (DUI) system in bivalved mollusks. In DUI, maternal F mtDNA is transmitted to daughters and sons and paternal M mtDNA is transmitted to sons (F vs. M DNA divergence >40%). Breton et al. recently discovered novel (in addition to the typical set of 13) sex-specific mt-encoded proteins in bivalves with DUI, and demonstrated that these proteins are exported from the mitochondria and likely play a role in sex determination. These results are of great value because they show that animal mtDNAs have a larger functional repertoire than previously thought and represent the first case of mtDNA-based sex determination in animals. This challenges textbook biology which state that mt-encoded proteins are uniquely found inside mitochondria to assist in energy production. However, the mechanisms underlying DUI and sex determination are still unknown and the cause of deviation from the strict maternal inheritance rule in bivalves remains an open question. The proposed research aims to better understand (i) the origin and evolution of DUI and the new mt-encoded genes and (ii) the genetic mechanisms that govern DUI and sex determinations in bivalves. This project investigates innovative and potentially transformative ideas in mitochondrial research that will interest a wide range of scientists exploring the fields of organellar inheritance, intergenomic conflict, and evolution of sex determination. It will provide the basis for the development of genetic markers for the manipulation of sex determination for selective breeding programs of economically important bivalves. This work will also shed light on the origin and functions of novel mt-encoded genes and could eventually have medical implications for therapy of mitochondrial diseases.

线粒体（mt）被称为“细胞的发电站”，因为它们负责动物细胞中大部分的能量生产。它们含有自己的DNA (mtDNA)，该DNA编码13种参与能源生产的蛋白质。mtDNA的突变是导致包括糖尿病和癌症在内的几种人类疾病的原因。动物mtDNA的遗传一直被认为是严格的母系遗传，直到在双壳类软体动物中发现了一种完全不同的双单亲遗传（dual Uniparental inheritance， DUI）系统。在DUI中，母亲的F mtDNA遗传给女儿和儿子，父亲的M mtDNA遗传给儿子（F与M的DNA差异为40%）。Breton等人最近在DUI双壳类动物中发现了新的（除了典型的13种）性别特异性mt编码蛋白，并证明这些蛋白从线粒体输出，可能在性别决定中发挥作用。这些结果具有重要的价值，因为它们表明动物mtdna具有比以前认为的更大的功能库，并且代表了动物中基于mtdna的性别决定的第一个案例。这对教科书生物学提出了挑战，教科书认为，mt编码的蛋白质是在线粒体内唯一发现的，以协助能量产生。然而，DUI和性别决定的机制仍然未知，双壳类动物偏离严格的母体遗传规则的原因仍然是一个悬而未决的问题。本研究旨在更好地了解双壳类动物DUI的起源和进化以及新的mt编码基因，以及控制DUI和性别决定的遗传机制。该项目研究了线粒体研究中的创新和潜在的变革思想，这将引起广泛的科学家在细胞器遗传、基因组间冲突和性别决定进化等领域的兴趣。这将为开发具有重要经济意义的双壳类生物选择性育种的遗传标记、操纵性别决定提供依据。这项工作还将揭示新的mt编码基因的起源和功能，并最终可能对线粒体疾病的治疗具有医学意义。