Causes and consequences of genetic variation in fitness

健康遗传变异的原因和后果

• 批准号: 251100-2008
• 负责人: Chippindale, Adam
• 金额: $ 2.99万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=514559
• 关键词: Causes; consequences; genetic; variation; fitness

Evolutionary Biology is undergoing radical transformation as its embrace extends ever further into the workings of the organism, the cell, and the genome. More and more, the genome appears to be not simply a well-ordered blueprint but a noisy 'parliament' of interacting genes. My research team studies the origins and nature of genetic variation using original and powerful techniques in the ordinary fruit fly, Drosophila. Our research has shown that levels of genetic variation related to survival and lifetime reproductive success are surprisingly high, given that these are the very components of Darwinian fitness. The proposed research uses special cloning methods to quantify three distinct sources of variation: spontaneous mutation, gene-gene interactions, and sexually antagonistic genes. First, we will suspend natural selection across the entire genome, allowing mutations to accumulate unchecked over many generations. Preliminary results show that mutations manifest themselves quickly, and the same mutations have a much more severe impact on males than females. Experiments will measure genetic variation in fitness over the full lifespan of the fly. We will characterize growth, reproduction, ageing and death in our lines, and investigate the controversial phenomenon of 'plateaus in senescence', in which ageing appears to stop late in life. Next, we will break apart the cloned genomes and assemble new mixtures to study the degree to which genes add together in effect or interact synergistically. Finally, in all experiments, we will measure the consistency of genetic effects in the two sexes and analyze for sexually antagonistic genes. Our research has implicated SA genes in reducing the average fitness of both females and males. This research is modular and scalable, facilitating the training of expert personnel at every level. It explores fundamental questions in evolutionary genetics, and ultimately provides insight into problems as diverse as genetic diseases, infertility, and senescence. By showing how fitness is governed in bottled flies, we hope to illuminate the workings of other genomes, notably our own, and shape understanding of a central question in Biology: why so much fitness-related variation?

进化生物学正在经历彻底的转变，因为它的拥抱进一步扩展到有机体，细胞和基因组的运作。越来越多的人认为，基因组似乎不仅仅是一个有序的蓝图，而是一个相互作用的基因的嘈杂的“议会”。我的研究团队研究遗传变异的起源和性质，使用原始和强大的技术在普通的果蝇，果蝇。我们的研究表明，与生存和终生繁殖成功相关的遗传变异水平惊人地高，因为这些正是达尔文适应性的组成部分。这项研究使用特殊的克隆方法来量化三种不同的变异来源：自发突变，基因-基因相互作用和性拮抗基因。首先，我们将暂停整个基因组的自然选择，允许突变在许多代中不受控制地积累。初步结果表明，突变很快就会显现出来，同样的突变对男性的影响比女性严重得多。实验将测量果蝇整个生命周期中适应性的遗传变异。我们将描述我们品系的生长、生殖、衰老和死亡的特征，并调查有争议的“衰老高原”现象，即衰老似乎在生命后期停止。接下来，我们将把克隆的基因组分开，组装新的混合物，以研究基因在多大程度上有效地结合在一起或协同地相互作用。最后，在所有的实验中，我们将测量遗传效应在两性中的一致性，并分析性拮抗基因。我们的研究表明SA基因降低了女性和男性的平均健康水平。这项研究是模块化和可扩展的，有利于各级专家人员的培训。它探讨了进化遗传学中的基本问题，并最终提供了对遗传疾病，不育和衰老等各种问题的见解。通过展示瓶装苍蝇的适应性是如何控制的，我们希望阐明其他基因组的运作，特别是我们自己的基因组，并形成对生物学中一个中心问题的理解：为什么有这么多与适应性相关的变异？