Chromosomal rearrangements as agents of speciation

尽管《物种起源》出版已有近150年，但我们对新物种是如何形成的仍然知之甚少。在哺乳动物中，许多密切相关的物种在染色体数目上存在差异（例如人类有46个，而黑猩猩有48个）;因此，人们认为染色体数目的变化可能与新物种的产生有关。染色体数目改变的一种方式是当两个近端着丝粒（“单臂”染色体，一端有一个称为着丝粒的结构）融合在一起形成一个中着丝粒（“双臂”染色体，中间有一个着丝粒）。这些后着丝粒细胞也可以与其他近端着丝粒细胞或后着丝粒细胞交换“手臂”。尽管家鼠通常只有近端着丝粒染色体，但欧洲有相当多的种群的小鼠具有染色体融合。当一个特定区域的所有家鼠都具有相同的融合集时，这个种群被称为“种族”。具有不同染色体组的两个种族（一个种族中的端着丝粒和另一个种族中的中着丝粒，或者两个种族中的不同的中着丝粒组）可以杂交。然而，在杂种中，在生殖细胞产生过程中，一个种族的染色体不能与另一个种族的染色体适当地相互作用（'减数分裂'），导致：1）生殖细胞和不可行的后代与错误的染色体数目，造成生育能力下降（即“杂种不育”）; 2）染色体之间正常的物质交换（“重组”）减少（即杂种显示“重组抑制”）。这两个问题可能会阻止杂交种族正确地交换基因，因此种族开始独立进化，并可能成为完全独立的物种。因此，通过研究家鼠的种族，有可能发现新的哺乳动物物种是如何起源的。在这个项目中，我们将继续我们在北方意大利长期进行的家鼠研究。我们将研究标准小鼠与近端着丝粒染色体和中间着丝粒种族之间的杂交，以及两种类型的中间着丝粒种族之间的杂交。我们想知道这些种族是否由于杂种不育或重组抑制或两者兼而有之而正在形成新物种。我们已经知道存在杂交不育，但我们不知道这是否足以阻止杂交种族正确交换基因。我们将使用分子技术来观察实验室饲养的杂种在减数分裂时的染色体交换，看看这是否受到限制，正如重组抑制的想法所预期的那样。对于这两种模型，我们可以预期基因独立进化，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，我们有一个完整的小鼠DNA序列（就像我们对人类一样），在小鼠染色体上的不同位置找到基因并不困难，我们可以用它来区分我们的两个模型。为了研究种族之间的遗传差异以及它们杂交时会发生什么，我们将从自然杂交区域收集小鼠。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能够为我们的两个模型提供不同的预测。通过这种方式，我们将能够确定是什么促进了家鼠的物种形成，并为我们提供了对整个哺乳动物这一过程的宝贵见解。

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.