Gut microbiome variation, fitness and senescence within a natural vertebrate population

在许多动物种群中，在繁殖成功、生存和衰老方面存在着广泛的个体差异，这一点是清楚的，然而，导致这种差异的原因在很大程度上仍未得到解释。了解这种差异的驱动因素非常重要，因为差异适应度是适应性进化的基础，而且这种理解可能有助于改善个体的健康和福祉。对人类和圈养动物的研究表明，肠道微生物组（一个由数千种物种组成的复杂微生物群落）组成的变化可以在宿主功能中发挥重要作用，影响消化、免疫和发育等成分，并影响有害状况和疾病的结果。研究还表明，随着年龄的增长，基因的变化可能在个体的衰退中起着因果作用。因此，鉴于转基因基因对宿主的健康似乎是不可或缺的，我们可以假设，转基因基因的变异将对个体的生存和繁殖成功产生重要影响。转基因变异也可能导致包括人类在内的人群中观察到的个体之间广泛且大部分无法解释的衰老差异。令人惊讶的是，在确定自然种群中个体之间存在多少转基因变异或哪些因素驱动这种变异方面，几乎没有开展任何工作。更重要的是，据我们所知，目前还没有研究确定个体转基因变异是否与野生脊椎动物种群的繁殖成功和衰老有关。鉴于非自然条件可以从根本上改变个体的转基因基因，并且个体与其环境之间的复杂相互作用影响生存和繁殖成功，如果我们要充分了解转基因变异的原因和适应性后果，自然条件下的研究是必不可少的。我们的目标是通过对细菌转基因个体变异的原因进行全面调查来填补这些知识空白，并首次研究这与自然脊椎动物种群中的适应性和衰老之间的关系。我们有完美的条件来做这件事，因为我们对塞舌尔莺的离散种群进行了长期研究，使我们能够在它们的一生中跟踪和取样。我们拥有个体一生中详细的环境、遗传、生物条件以及准确的生存和繁殖成功数据（不受分散影响）。我们也有一个人口的10代遗传谱系，结合社会亲子关系的对比模式（例如，由于不忠），为转基因特征的遗传性分析提供了有力的基础。重要的是，我们的nerc资助的试点研究成功地测试了粪便样本中转基因变异的测序和分析方案，我们的结果证实了这个群体中存在相当大的转基因个体差异。我们现在已经万事俱备，以促进这项新颖而及时的研究取得成功。评估野生种群中存在的自然共变是揭示转基因进化重要性的必要步骤。这一建议将使我们能够确定自然选择所需的组成部分——个体变异、与该变异相关的差异适应度以及该变异的遗传——是否存在于自然种群中的转基因中。这些证据将首次为脊椎动物宿主的自然选择是由转基因介导的这一观点提供强有力的支持。从应用的角度来看，了解转基因变异的原因和后果也很重要，因为它将告诉我们如何管理转基因多样性，以优化我们自己的健康，以及我们利用或希望保护的动物的特征和状况。

That extensive individual variation in reproductive success, survival and senescence (ageing) exists in many animal population is clear, however what causes this variation remains largely unexplained. Understanding the drivers of this variation is of great importance, both because differential fitness is the basis of adaptive evolution, but also because such understanding may help improve the health and wellbeing of individuals.Studies on humans and captive animals have shown that variation in the composition of the gut microbiome (GM) - a complex microbial community comprising thousands of species - can play an important role in host function, influencing components such as digestion, immunity and development, and affecting the outcome of deleterious conditions and disease. Research has also suggested that changes in the GM can play a causal role in an individual's deterioration with age. Therefore, given that the GM appears to be integral to the health of its host, we can hypothesise that variation in the GM will have important consequences for an individual's survival and reproductive success. GM variation may also contribute to the extensive, and largely unexplained, differences in senescence observed among individuals within populations, including in humans. It is then surprising that so little work has been undertaken to determine how much GM variation exists among individuals within natural populations, or which factors drive this variation. More importantly, to our knowledge no studies have yet determined if individual GM variation is associated with reproductive success and senescence within a wild vertebrate population. Given that unnatural conditions can radically change an individual's GM, and complex interactions between the individual and its environment influence survival and reproductive success, studies under natural conditions are essential if we are to fully understand the causes and fitness consequences of GM variation.We aim to fill these gaps in our knowledge by undertaking a comprehensive investigation of the causes of individual variation in the bacterial GM, and, for the first time, how this is linked to fitness and senescence within a natural vertebrate population. We are perfectly placed to do this because our long-term study of a discrete population of the Seychelles warbler Acrocephalus sechellensis, allows us to follow and sample individuals throughout their lives. We have detailed environmental, genetic, biological condition and accurate survival and reproductive success data (unconfounded by dispersal) on individuals across their lives. We also have a 10-generation genetic pedigree of the population which, combined with contrasting patterns of social parentage (e.g. due to infidelity), provides the basis for a powerful analysis of the heritability of GM characteristics. Importantly, our NERC-funded pilot study successfully tested protocols for the sequencing and analysis of GM variation from faecal samples, and our results confirm that considerable individual variation in the GM exists within this population. We now have everything in place to facilitate the success of this novel and timely study.Assessing the natural co-variation that exists in a wild population is an essential step in exposing the evolutionary importance of the GM. This proposal will allow us to determine if the components required for natural selection - individual variation, differential fitness linked to that variation, and inheritance of that variation - exist in terms of the GM within a natural population. Such evidence would, for the first time, provide strong support for the idea that natural selection on vertebrate hosts is mediated by the GM. Knowledge of the causes and consequences of GM variation is also important from an applied perspective as it will inform how we can manage GM diversity to optimise our own health, and the traits and condition of the animals that we utilise or wish to conserve.