Chromosomal rearrangements as agents of speciation

尽管《物种起源》发表于近150年前，但我们仍然对新物种是如何形成的知之甚少。在哺乳动物中，许多密切相关的物种在染色体数量上存在差异(例如，人类有46条染色体，而黑猩猩有48条)；因此，人们认为染色体数量的变化可能与新物种的产生有关。染色体数目变化的一种方式是当两个端着丝粒(一端有着丝粒结构的单臂染色体)融合在一起形成中着丝粒(两臂染色体，着丝粒在中间)。这些超着丝点也可以与其他完全着丝点或超着丝点互换“手臂”。虽然家鼠通常只有顶端着丝粒染色体，但在欧洲有相当多的种群的小鼠有染色体融合。当一个特定地区的所有家鼠都有相同的融合集时，这个种群被称为“种族”。具有不同染色体组的两个种族(一个种族的顶着丝粒和另一个种族的着丝粒，或者两个种族的不同的着丝粒集合)可以进行杂交。然而，在杂交种中，一个种族的染色体在生殖细胞生产期间不能与另一个种族的染色体正确地相互作用(“减数分裂”)，这导致：1)生殖细胞和染色体数目错误的不能存活的后代，导致生育力降低(即“杂交不育”)；2)染色体之间正常的物质交换(“重组”)减少(即杂交种表现出“重组抑制”)。这两个问题可能会阻止杂交小种正确地交换基因，从而使小种开始独立进化，并可能成为完全不同的物种。因此，通过研究家鼠的种族，可能会发现新的哺乳动物物种是如何起源的。在这个项目中，我们将继续我们在意大利北部进行的长期家鼠研究。我们将检查具有端着丝粒染色体的标准小鼠和中着丝粒小种之间的杂交，以及两种类型的中着丝粒小种之间的杂交。我们想知道这些小种是由于杂交不育或重组抑制，还是两者兼而有之，正在形成新物种的道路上。我们已经知道有杂交不育，但我们不知道这是否足以阻止杂交种族正确地交换基因。我们将使用分子技术来观察实验室饲养的杂交后代减数分裂时的染色体交换，看看这是否像重组抑制想法所预期的那样受到限制。对于这两种模型，我们可能期望基因独立进化，但对于重组抑制模型，我们预测它将发生在减数分裂时不能正确交换的染色体区域，即使没有生育问题。幸运的是，我们有小鼠的完整DNA序列(就像我们对人类的DNA序列一样)，而且在小鼠染色体上的不同位置找到基因并不困难，我们可以用来区分我们的两个模型。为了研究不同种族之间的遗传差异以及它们杂交时会发生什么，我们将从杂交的自然区域收集老鼠。我们的大部分研究将深入分析这些小鼠染色体的特定区域，选择染色体是因为它们有能力为我们的两个模型提供不同的预测。通过这种方式，我们将能够决定是什么促进了家鼠的物种形成，并让我们对哺乳动物的这一过程有了宝贵的洞察。

Although 'The Origin of Species' was published almost 150 years ago, we still understand little about how new species are formed. In mammals, many closely related species differ in chromosome number (e.g. humans have 46 while chimpanzees have 48); therefore, it is thought that a change in chromosome number could be involved in the generation of new species. One way in which chromosome numbers can change is when two acrocentrics ('one-armed' chromosomes with a structure known as the centromere at one end) fuse together to form a metacentric ('two-armed' chromosomes with the centromere in the middle). These metacentrics can also exchange 'arms' with other acrocentrics or metacentrics. Although house mice usually have only acrocentric chromosomes, there are quite a few populations in Europe where the mice have chromosome fusions. When all the house mice in a particular area have the same set of fusions, this population is called a 'race'. Two races with different sets of chromosomes (either acrocentrics in one race and metacentrics in the other, or different sets of metacentrics in the two races) can interbreed. However, in the hybrids the chromosomes of one race cannot interact properly with the chromosomes of the other race during germ-cell production ('meiosis') which leads to: 1) germ cells and unviable offspring with the wrong number of chromosomes, causing reduced fertility (i.e. 'hybrid infertility'); 2) a reduction in the normal exchange of material ('recombination') between chromosomes (i.e. hybrids display 'recombination suppression'). Both these problems may stop the hybridising races from swapping genes properly, so that the races start to evolve independently and may become completely separate species. Therefore, by studying races of house mice, it may be possible to discover how new mammalian species originate. In this project, we will continue our long-running research of house mouse in Northern Italy. We will examine hybridisation between the standard mice with acrocentric chromosomes and a metacentric race, and hybridisation between two types of metacentric race. We would like to know whether these races are on the way to forming new species as a result of hybrid infertility or recombination suppression, or both. We already know that there is hybrid infertility, but we do not know if it is enough to stop hybridising races from swapping genes properly. We will use molecular techniques to look at chromosome exchange at meiosis in laboratory-reared hybrids, to see if this is restricted, as expected with the recombination suppression idea. For both models we may expect genes to evolve independently, but for the recombination suppression model we predict that it will occur in the chromosome regions that do not exchange properly at meiosis even if there are no fertility problems. Luckily, we have a complete DNA sequence for the mouse (just as we have for humans), and there is no difficulty in finding genes at various positions on mouse chromosomes, that we can use to distinguish between our two models. To examine the genetic differences between the races and what happens when they hybridise, we will collect mice from natural areas of hybridisation. Much of our study will be an in depth analysis of particular regions of chromosomes of these mice, with the chromosomes selected for their ability to give us different predictions for our two models. In this way, we will be able to decide what may be promoting species-formation in the house mouse, and give us valuable insight into this process for mammals in general.