The prevalence of genetic introgression in speciation

背景：物种间遗传交换的重要性（即来自一个物种的基因渗入） 通过杂种中间体变成另一种物种）是进化论界争论的一个持续话题 生物学家。虽然一些人声称基因交换很普遍，但另一些人则声称这种情况极其罕见。目前， 几乎没有定量数据支持这两种情况。 广泛的长期目标：拟议的自然混合区研究将量化 物种之间基因交换的普遍性，以了解频率和进化后果 的基因交换。该提案利用混合区的这些自然实验来寻找混合 基因组，我可以用它来绘制杂交个体之间不同的复杂行为特征的遗传学图谱 种。由于行为特征的遗传图谱已被证明通过传统方法非常困难，因此混合 绘图提供了在这些重要问题上取得进展的独特机会。 具体目标：该研究的目标 1 是绘制六个自然杂交区域（其中四个区域）的基因渗入流行率图。 这是第一次在这里记录。目标 2 将使用来自混合区的混合果蝇来绘制基因图谱 温度偏好这一重要的生态特征的基础。目标 3 将使用来自另一个的混合苍蝇 杂交区域来绘制配偶偏好复杂行为特征背后的基因图谱。 方法：可以在自然栖息地收集果蝇属果蝇并进行维护 在实验室条件下，并拥有无与伦比的分子遗传学和基因组工具库。这个 该提案提出了一种用于识别基因组中渗入等位基因的新模型，这种方法仅 在两个亲本物种都具有高质量基因组组装的杂交生物体中是可行的。的 在这些混合物分析中鉴定出的基因将通过 CRISPR 介导的基因进行功能验证 替代品。混合物作图和基因组编辑的初步结果都充满希望。 健康相关性：人类的混合物图谱是用于识别健康的主要方法 致病基因变异。然而，后续实验来测试与相关基因的功能 疾病不能在人类身上进行。因此，混合物映射协议从未得到验证 从识别与疾病相关的变异的群体水平到功能性的端到端 表现型状态的分子遗传水平。这个提议之所以具有创新性，是因为它 开发新的计算方法来识别具有复杂祖先的基因组区域，然后连接 通过基因组编辑将这些基因组模式转化为可测量的表型差异。 影响：这项研究的结果将提供第一个关于渗入模式的广泛观点，其中 物种在自然界中杂交，并将利用这些混合模式来剖析物种的遗传基础 导致生殖隔离的物种之间的行为差异。

Background: The importance of genetic exchange between species (i.e. introgression of genes from one species into another through hybrid intermediates) is a constant subject of debate among evolutionary biologists. While some claim genetic exchange is pervasive, others claim that it is extremely rare. Currently, there is little data quantitatively supporting either of these scenarios. Broad, long-term objective: The proposed study of naturally occurring hybrid zones will quantify the prevalence of genetic exchange between species to understand the frequency and evolutionary consequences of gene exchange. The proposal takes advantage of these natural experiments in hybrid zones to find admixed genomes with which I can map the genetics of complex behavior traits that differ between the hybridizing species. Since genetic mapping of behavior traits has proven very difficult by conventional means, admixture mapping provides a unique opportunity to make progress on these important questions. Specific aims: Aim 1 of the study is to map the prevalence of introgression in six natural hybrid zones, four of which are documented here for the first time. Aim 2 will used admixed flies from a hybrid zone to map genes underlying the ecologically important trait of temperature preference. Aim 3 will use admixed flies from another hybrid zone to map genes underlying the complex behavioral trait of mate preference. Method: Fruit flies from the genus Drosophila can be collected in their natural habitat and also maintained under laboratory conditions, and have an unmatched arsenal of molecular genetic and genomic tools. This proposal presents a novel model for identifying introgressed alleles in the genome, an approach that is only feasible in hybridizing organisms for which both parental species have high quality genome assemblies. The genes identified in these admixture analyses will be functionally validated with CRISPR-mediated gene replacements. Preliminary results for admixture mapping and genome editing are both promising. Health-relatedness: Admixture mapping in humans is a primary approach used for the identification of disease-causing gene variants. However, follow up experiments to test the function of genes correlated with disease cannot be performed in humans. Admixture mapping protocols have therefore never been validated end-to-end from the population level at which variants correlated with disease are identified, to the functional molecular genetic level where the phenotypic state is manifested. This proposal is innovative because it develops new computational methods to identify genomic regions with complex ancestry, and then connects these genomic patterns to measurable phenotypic differences via genome editing. Impact: The results from this study will provide the first broad view of patterns of introgression in cases where species interbreed in nature, and will leverage those patterns of admixture to dissect the genetic basis of behavioral differences between species that cause reproductive isolation.