Deciphering the genomic signatures of speciation and introgression

随着物种的分化，它们的基因组也会分化。然而，这种可以通过比较序列直接测量的遗传差异具有很大的随机性。首先，存在于祖先物种中的遗传多样性随机传递给其后代，并可以长期存活。其次，在初始分裂后可能存在遗传交换，这进一步增加了遗传分化的方差。能够以多种方式对这两个过程进行建模是很重要的：首先，研究人员往往希望对密切相关物种的历史做出推断，并理想地确定导致它们与基因组序列背道而驰的因素。例如，了解我们自己的祖先是否在尼安德特人相遇的地方与尼安德特人杂交将是一件有趣的事情。由于物种形成是在进化的时间尺度上发生的，因此从基因组数据进行这种间接推断往往是研究这一过程的唯一途径。其次，人们对确定基因组中可能在物种之间和物种内进行选择的区域非常感兴趣。在最近分化的物种中，这可以告诉我们哪些基因参与了分化，并提供了关于物种形成机制以及基因组结构和地理分离的作用的线索。最后，新生物种之间的基因流动或渗透本身可能是适应性的。例如，与独立进化相比，对杀虫剂的抗药性可以从已经进化出这一特征的近亲那里更快地获得。为了有希望识别涉及特定基因的导入或选择，我们需要确切地知道不同物种之间的不同情况对基因组中中性多样性的模式有什么影响。然而，区分即使是最简单的历史也需要大量数据，而且事实证明，这是出了名的困难。随着测序技术的快速发展，我们对物种分化做出推断的能力现在受到理论而不是数据的限制。我将开发新的统计方法，使我们能够直接和准确地从基因组数据中估计两个物种之间分歧的关键参数，特别是它们的分裂时间以及它们之间的基因流动的数量和方向。这些方法将被应用于果蝇的三个岛种的基因组数据：D sechellia，D mauritiana和D santomea，它们是较近(250-50万年前)从大陆祖先分离出来的，可以被视为非常相似的地理和生态环境中物种形成的独立复制。这些物种是独一无二的，因为实验室研究揭示了大量涉及生殖隔离的特征的遗传基础，包括导致杂交不育的基因，以及那些潜在的更复杂的特征，如交配行为。然而，他们实际的分歧历史鲜为人知，因为目前的推理方法仅限于小数据集。特别是，我们不知道在分化过程中或分化后的基因流有多重要。新的统计方法将使我能够以多种方式比较这三个模型系统中物种形成的历史。首先，我会问，离大陆较近的岛屿上的物种与大陆近亲之间的基因交流是否比距离较远的物种更多。其次，我将测试当前物种形成模型预测的基因组不同区域之间的差异是否存在差异，以及这些差异是物种特有的还是普遍存在的。最后，我将调查已知的负责生殖隔离的基因是否可以仅通过它们不同的分化模式就在基因组背景下区分开来。这将使在其他生物中识别此类基因成为可能，而这些生物的功能知识无法通过简单的基因组扫描获得。

As species diverge, so do their genomes. However, this genetic divergence, which can be measured directly by comparing sequences, has a large random component. Firstly, genetic diversity present within an ancestral species is passed on to its descendants at random and can survive for a long time. Secondly, there may be genetic exchange after the initial split, which further increases the variance in genetic divergence. Being able to model both processes matters in many ways: Firstly, researchers are often want to make inferences about the history of closely related species and ideally identify the factors that caused them to diverge from their genome sequence. For example, it would be interesting to know whether our own ancestors hybridized with Neanderthals in places where they met. Since speciation happens over evolutionary timescales, such indirect inferences from genomic data are often the only way to study the process. Secondly, there is great interest in identifying regions of the genome that may have been under selection both between and within species. In the case of recently diverged species this can tell us which genes were involved in divergence and provides clues about the mechanisms of speciation and the roles of genome structure and geographic separation. Finally, gene flow or introgression between nascent species may be adaptive itself. For example, resistance to insecticide can be acquired more rapidly from close relatives that have already evolved this trait than through independent evolution. To have any hope to identify introgression or selection involving particular genes, we need to know exactly what effects different scenarios of divergence between species have on patterns of neutral diversity in the genome. However, distinguishing between even the simplest histories requires large amounts of data and has proven notoriously difficult. With the rapid advances in sequencing technology, our ability to draw inferences about species divergence is now limited by theory rather than data. I will develop new statistical methods that allow us to estimate key parameters of the divergence between two species, in particular their splitting time and the amount and direction of gene flow between them directly and exactly from genomic data. These methods will be applied to genomic data from three island species of Drosophila: D sechellia, D. mauritiana and D. santomea which have split from their mainland ancestors relatively recently (250-500,000 years ago) and can be seen as independent replicates of speciation in very similar geographic and ecological settings. These species are unique because lab studies have revealed much about the genetic basis of a large range of traits involved in reproductive isolation, including genes that cause hybrids to be infertile and those underlying more complicated traits such as mating behaviour. However, their actual history of divergence is poorly known because current inference methods are limited to small datasets. In particular, we do not know how important gene flow during or after divergence has been. The new statistical method will allow me to compare the history of speciation in these three model systems in a number of ways. Firstly, I will ask whether species on islands closer to the mainland have experienced more genetic exchange with their mainland relatives than those further away. Secondly, I will test if divergence differs between different regions of the genome as predicted by current models of speciation and whether these differences are species-specific or universal. Finally, I will investigate whether genes known to be responsible for reproductive isolation can be distinguished against the genomic background by their different patterns of divergence alone. This would make it possible to identify such genes in other organisms where functional knowledge is not available through simple genomic scans.