Comparative genome mapping of the Anopheles species cluster

描述(由申请人提供)：针对负责媒介能力的基因是控制传染病的一种新方法。为了更好地了解媒介能力的遗传决定因素，并在媒介生物学家和疟疾社区成员的支持下，NHGRI和NIAID资助了16种按蚊(http://www.broadinstitute.org/annotation/genome/anopheles).的基因组和转录体的测序随着基因组序列的出现，研究人员现在有了独特的机会来进行比较分析，以推断与载体能力相关的进化变化。这个R21项目的主要目标是为三个主要的疟疾媒介开发基于染色体的参考基因组组件：An。Arabiens，An.Stephensi和An.白血球。草图基因组组件可用于这些物种(https://olive.broadinstitute.org/comparisons/anopheles.1).我们的项目是及时的，因为它将为新测序的按蚊物种创造关键的基因组工具。该项目具有创新性，因为它将使用自动多色荧光原位杂交(AM-FISH)和自动显微分析。我们将首次通过全基因组基因序列分析来进行按蚊的系统发育分析，并对染色体重排的模式和机制获得重要的见解。先进设备的可获得性以及PI在细胞遗传学和比较基因组分析方面的专业知识将确保成功实现该项目的目标。该提案有三个具体目标。具体目标1.将测序支架物理定位到染色体上。Arabiens，An.Stephensi和An.白血球。具体目的2.重建按蚊属基因组尺度的重排系统发育。对象中所有已修复反转的断点。Arabiens，并将完善An的染色体系统发育。冈比亚亚纲复合体。Stephensi和An.白线虫为外类群种。具体目的3.确定按蚊属染色体进化的模式和机制。我们将检验这样的假设：(I)尽管倒位多态很少，但X染色体具有最高的倒位固定率，以及(Ii)倒位具有染色体特定和物种特定的起源机制和固定率。好了！

DESCRIPTION (provided by applicant): Targeting genes responsible for vectorial capacity is a novel approach to controlling infectious diseases. To develop a better understanding of genetic determinants of vectorial capacity and with support from vector biologists and members of the malaria community, NHGRI and NIAID have funded the sequencing of the genomes and transcriptomes of 16 Anopheles species (http://www.broadinstitute.org/annotation/genome/anopheles). With genome sequences becoming available, researchers now have the unique opportunity to perform comparative analysis for inferring evolutionary changes relevant to vector ability. However, success of these comparative genomic analyses will be limited, and inferences about evolution of the vectorial capacity traits will be less informative if researchers deal with numerous sequencing scaffolds rather than with chromosome-based genome assemblies. The major goal of this R21 project is to develop chromosome-based reference genome assemblies for three major malaria vectors: An. arabiensis, An. stephensi, and An. albimanus. Draft genome assemblies are available for these species (https://olive.broadinstitute.org/comparisons/anopheles.1). Our project is timely because it will create crucial genomic tools for the newly sequenced Anopheles species. The project is innovative because it will use the automated multicolor fluorescent in situ hybridizatio (AM-FISH) and automated microscopic analysis. We will, for the first time, perform phylogenetic analysis of anopheline mosquitoes by genome-wide gene order analysis and gain important insights into patterns and mechanisms of chromosomal rearrangements. The availability of state-of-the-art equipment and the expertise of the PI in cytogenetics and comparative genomic analysis will ensure successful achievement of the project's goal. The proposal has three specific aims. Specific Aim 1. Physically map sequencing scaffolds to chromosomes of An. arabiensis, An. stephensi, and An. albimanus. We will place and orient scaffolds to polytene chromosomes by AM-FISH, thus, creating chromosome-based reference genome assemblies for the species belonging to the series Pyretophorus (subgenus Cellia), series Neocellia (subgenus Cellia), and series Albimanus (subgenus Nyssorhynchus), respectively. Specific Aim 2. Reconstruct genome-scale rearrangement phylogeny of genus Anopheles. We will identify breakpoints of all fixed inversions in An. arabiensis and will refine the chromosomal phylogeny in the An. gambiae complex using An. stephensi and An. albimanus as outgroup species. Specific Aim 3. Determine the pattern and mechanisms of chromosome evolution in genus Anopheles. We will test the hypotheses that (i) the X chromosome has the highest rate of inversion fixation despite the paucity of inversion polymorphisms, and (ii) inversions have chromosome-specific and species-specific mechanisms of origin and rates of fixation. !