Molecular evolution and variation in genomic regions with low recombination

生物学的经典问题之一是有性繁殖的进化作用。这涉及到将双亲的基因组聚集在一起，并通过被称为基因重组的过程重新洗牌，这样单个后代就会从每个父母那里获得混合的贡献。这使得基因组中不同位置的遗传变异的进化命运或多或少相互独立。这样做的一个结果是，自然选择可以在基因组的一个位置上发挥作用，而不会干扰其他位置上发生的事情。已经提出了许多具体的进化过程模型，这些模型可能会在不同地点之间造成无性时的干扰：它们都预测，在无性的情况下，选择的效率会降低，从而导致适应度的大幅下降。然而，很难在自然界中检验这些预测，因为无性物种或种群非常罕见，而且在大多数情况下，只是最近才出现在有性祖先身上。然而，验证这些预测是很重要的，这既是为了理解有性繁殖在自然界如此普遍的学术兴趣，也是因为有计划开发用于育种作物的无性植物品系。绕过这一困难的一种方法是比较同一基因组的不同区域。基因重组是在有性繁殖过程中造成父母贡献重新洗牌的过程，在基因组的某些部分很少见，甚至不存在，特别是基因组中被称为异染色质的部分。就进化模式而言，基因组的这些部分预计会表现得像无性物种。然而，直到最近，异染色质还不可能在DNA序列水平上进行研究，因为它包含大量反复重复的DNA，这使得在序列水平上进行研究变得困难。果蝇是研究最深入的模式动物物种，最近在果蝇研究方面的突破导致了数百个异染色质基因的特征。这意味着我们现在可以研究异染色质基因的进化和变异，几乎和基因组其他部分的基因一样容易，因此可以看到它们是否显示出预期的模式，因为它们缺乏重组。有先进的统计方法可用于这一目的，但需要有效地使用大型数据集。我们计划开发新的DNA测序技术，这种技术可以快速而廉价地产生大量信息。我们将使用这些来生成关于异染色质和基因组其他部分中大量基因的可变性的数据，在两个密切相关的果蝇物种的种群中。通过将这些研究的结果与对其他果蝇物种已发表的基因组序列的计算机分析相结合，我们将能够确定我们在基因组低重组水平区域看到的模式是否与我们的理论模型相符。如果是这样的话，我们将拥有比目前更令人信服的证据，证明有性繁殖具有进化优势，并且缺乏性行为会导致健康状况严重下降。我们产生的数据也可以用来回答广泛的其他问题，例如异染色质中有多大程度的重组，自然选择对不参与确定蛋白质序列的DNA序列的作用程度，以及作用于蛋白质序列本身的选择强度。我们将通过数据库、科学出版物和会议公开这些数据。鉴于公众对这类问题的极大兴趣，我们也会向媒体通报我们的结果。

One of the classical problems of biology is the evolutionary role of sexual reproduction. This involves the bringing together of the genomes of two parents, and reshuffling them by the process known as genetic recombination, so that an individual offspring receives a mixture of contributions from each parent. This allows the evolutionary fates of genetic variants at different places in the genome to behave more or less independently of each other. One consequence of this is that natural selection can act at one site in the genome without interfering with what happens at other sites. Many specific models of evolutionary processes that can cause interference between different sites when sex is absent have been proposed: they all predict that selection is less effective in the absence of sex, leading to a large loss in fitness. It is, however, hard to test these predictions in nature, since asexual species or populations are very rare, and in most cases have arisen only recently from sexual ancestors. Nevertheless, it is important to test these predictions, both for the intellectual interest in understanding why sexual reproduction is so common in nature, and because there are plans to develop asexual strains of plants for the purpose of breeding crops. A way around this difficulty is to compare different regions of the same genome. Genetic recombination, the process that creates the reshuffling of parental contributions during sexual reproduction, is rare or absent in some parts of the genome, especially the part of the genome known as the heterochromatin. Such parts of the genome are expected to behave like asexual species, in terms of their evolutionary patterns. Until very recently, however, the heterochromatin has been impossible to study at the level of DNA sequences, since it contains large amounts of DNA that are repeated over and over again, making it hard to study at the sequence level. Recent breakthroughs in research on the fruitfly Drosophila, the best-studied model animal species, have led to the characterisation of several hundred genes in the heterochromatin. This means we are now in a position to study evolution and variation of genes in the heterochromatin almost as easily as genes in the rest of the genome, and can therefore see whether or not they show the patterns expected from their lack of recombination. Sophisticated statistical methods are available for this purpose, but require large datasets to be used effectively. We plan to exploit new technologies for sequencing DNA, which allow large quantities of information to be generated rapidly and cheaply. We will use these to generate data on variability in a large number of genes in the heterochromatin and in other parts of the genome, within populations of two closely related species of Drosophila. By combining the results of these studies with computer-based analyses of the published genome sequences of other species of Drosophila, we will be able to determine whether or not the patterns that we seen in regions of the genome with low levels of recombination agree with our theoretical models. If they do, we will have much more convincing evidence than currently exists that sexual reproduction has an evolutionary advantage, and that an absence of sex leads to a severe decline in fitness. The data that we generate can also be used for answering a wide range of other questions, such as the extent to which there is any recombination in the heterochromatin, the extent to which natural selection acts on DNA sequences that are not involved in determining protein sequences, and the intensity of selection acting on the protein sequences themselves. We will make these data publicly available through databases, scientific publications and conferences. Given the great public interest in questions of this kind, we will also communicate our results to the media.