Functional significance and regulation of the reproductive 'transferome'

即使是非常简单的生物也需要协调它们的活动。例如，海葵有一个简单的神经元网络，它可以控制体壁内的运动。随着生物体复杂性的增加，需要协调控制身体过程的例子越来越多。我们通常知道很多关于这些系统中的各个组件如何工作的信息。然而，我们严重缺乏关于基因产物如何以高度精确和灵活的方式控制的知识。这就是系统生物学，并且被认为是了解我们周围复杂世界的一种越来越重要的方法。我们的重点是一组与精子一起沿着转移的至关重要的精液蛋白-“转移蛋白”。几十年来，人们已经认识到精液蛋白质远不止是一个简单的精子缓冲器。事实上，它们可以对女性的行为和生理产生深远的影响。这些影响在果蝇中得到了最好的研究，我们在这里使用果蝇作为模型系统。然而，类似的影响也出现在各种各样的动物类群中。最近有报道，人类男性精液蛋白的转移引起女性宫颈免疫基因表达的变化。这被认为是为子宫着床做准备，以及保护免受性传播感染。在果蝇中，大约有130种精液蛋白组成了转移组。它们主要在雄性附腺（相当于人类雄性前列腺）、射精管和睾丸中产生。它们导致了各种各样的至关重要的影响：它们导致雌性产更多的卵，吃更多的食物（和不同类型的食物），对雄性的性接受程度降低，打开免疫基因，保留更多的精子储存，改变水平衡模式，睡眠减少！我们还从自己的工作中了解到，男性可以以高度复杂和个人灵活的方式对他们的社会和性环境做出反应。当雄性暴露在竞争对手面前时，当它们遇到雌性时，它们交配的时间更长，并且在这些更长的交配期间转移更多的转移组成分。这导致了更多的后代。此外，最近有证据表明，转移组的组成可以改变，以响应社会环境。尽管转移组的重要性，男性和女性和它的高度灵活性，我们几乎不知道它是如何控制的。然而，我们已经收集了强大的背景数据，并在果蝇有很好的实验工具来解决这个遗漏，给了我们一个独特的和无与伦比的机会，调查第一次控制这个复杂而重要的system.We假设，一个有效的方式来调节130个单独的组件的transferome是管理他们在'集'由相同的激活/灭活控制。这有助于在需要时迅速协调地释放各组物质，而不是试图从头开始单独制造它们。我们预测，这种控制水平在实践中是通过打开基因表达的转录因子和不同类型的小RNA来实现的，这些小RNA然后结合、抑制和“管理”基因组。我们的调查提供了与这些预测一致的有力证据。我们在这里提出的是通过实验直接改变这些不同类型的基因调控并测试对转移组的控制和功能的影响来对这些想法进行重要的测试。这将阐明如何可以稳健、精确和灵活地调节转移组。

Even very simple creatures need to co-ordinate their activities. For example, the sea anemone has a simple net of connected neurons with which it can control the movements within its body wall. As organisms increase in complexity, there are ever more examples where coordinated control of bodily processes is required. We often know a lot about how individual components in these systems might function. However, we have a serious lack of knowledge about how groups of gene products are controlled in the highly precise and flexible way they often are. This is systems biology and is recognized as an increasingly important way in which to understand the complex world around us.Our focus is on a group of vitally important semen proteins transferred along with sperm - the 'transferome'. It has been realized for many decades seminal fluid proteins are far more than a simple sperm buffer. In fact they can cause profoundly important effects on female behaviour and physiology. These effects have been best studied in the fruitfly, which we use as the model system here. However, similar effects are also seen across a huge variety of animal taxa. It has been reported recently that the transfer of seminal fluid proteins by human males causes changes in the expression of immune genes in the female cervix. This is thought to prepare the womb for implantation as well as protecting against sexually transmitted infections.In the fruitfly there are about 130 semen proteins making up the transferome. They are made mostly in the male accessory glands (the fly equivalent of the human male prostate) the ejaculatory ducts and a few in the testes. They result in a huge variety of vitally important effects: they cause females to lay more eggs, to eat more (and of different types of foods), to be less sexually receptive to males, to switch on immune genes, to retain more sperm in storage, to show altered patterns of water balance and to sleep less! We also know from our own work that males can respond in a highly sophisticated and individually flexible manner to their social and sexual environment. When males are exposed to rivals they mate for longer when they meet a female and transfer more transferome components during those longer matings. This results in a higher number of offspring. Furthermore, there is recent evidence to show that the composition of the transferome can change in response to social context.Despite the importance of the transferome to both males and females and its high degree of flexibility, we know next to nothing about how it is controlled. However, we have gathered strong background data and have excellent experimental tools in the fruitfly to tackle this omission, giving us a unique and unparalleled opportunity to investigate for the first time the control of this complex and important system.We hypothesise that an effective way to regulate 130 individual components of the transferome is to manage them in 'sets' controlled by the same activator / inactivator. This facilitates the quick and co-ordinated release of groups of substances as soon as they are required, rather than trying to make them all individually from scratch. We predict that this level of control is achieved in practice by transcription factors that turn on the expression of genes and by different types of small RNAs that then bind to, repress and 'manage' gene sets. Our investigations provide strong evidence that is consistent with these predictions. What we propose here are important tests of these ideas by experimentally altering directly these different types of gene regulation and testing the effects on the control and function of the transferome. This will elucidate how it is that the transferome can be regulated with robustness, precision and flexibility.