Chromosomal Phylogeny of the Anopheles gambiae Complex

冈比亚按蚊复合体的染色体系统发育

• 批准号: 7570777
• 负责人: IGOR V SHARAKHOV
• 金额: $ 21.8万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-07 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7570777
• 关键词: Anopheles gambiae; Asians; Behavior; Behavioral; Blood; Chromosomes; Chromosomes, Human, 1-3; Complex; Conflict (Psychology); Development; Evolution; Gene Duplication; Genes; Genetic; Genetic Polymorphism; Genomics; Goals; Habitats; Human; Knowledge; Malaria; Maps; Minor; Molecular; Molecular Cytogenetics; Phylogenetic Analysis; Phylogeny; Population; Population Replacements; Positioning Attribute; Relative (related person); Repetitive Sequence; Research; Sequence Homologs; Structure; Time; Trees; base; comparative; genome sequencing; member; molecular marker; novel strategies; public health relevance; transmission process; vector

DESCRIPTION (provided by applicant): Morphologically indistinguishable members of the Anopheles gambiae complex have remarkably distinct ecological adaptations, geographical distributions, and behaviors. This complex includes the major malaria vectors (A. arabiensis, A. gambiae), as well as minor vectors (A. bwambae, A. melas, A. merus) and nonvectors (A. quadriannulatus A, A. quadriannulatus B). Development of novel approaches to malaria management implies finding the ways to interrupt transmission by replacing populations of vectors with nonvectors. Our current knowledge about differences in genetic make-up among vectors and nonvectors is insufficient for implementing the successful population replacement. Inferring ancestral genomic features in the A. gambiae complex is crucial in identifying the evolutionary changes associated with the origin and loss of human blood choice, ecological and behavioral adaptations, and association with human habitats. These genomic changes should be targeted and manipulated so that malaria transmission can be reduced and eventually eliminated. Despite the availability of molecular markers and the genome sequence for A. gambiae, the phylogenetic relationships among the members are not fully resolved. Because of the recent origin of the complex, the high level of sequence similarity, genetic introgression, and shared molecular ancestral polymorphisms confound the ability to determine the direction of evolution unambiguously. The major goal of this exploratory R21 project is to determine the ancestral and derived chromosomal arrangements in the A. gambiae complex. The advantage of our approach is that it is based on observations that the ancestral arrangements are shared between ingroup and outgroup species and that the breakpoint structure can indicate the direction of chromosomal evolution. We plan to (1) identify chromosomal arrangements shared between the A. gambiae complex and the outgroup species A. stephensi and (2) determine derived structural features of inversion breakpoints such as the presence of transposable/repetitive elements and gene duplications. The comparative analysis of the ingroup and outgroup breakpoints will for the first time assess the uniqueness of the inversions and unambiguously determine the ancestral X and 2R arrangements in the complex. Although identifying and sequencing breakpoints are technically challenging tasks, the successful characterization of the 2La breakpoints and our preliminary studies suggest that our research aims are achievable. Our proposal has two specific aims: 1. To physically map the breakpoints of fixed inversions Xag, Xbcd, 2Rop to the chromosomes of the A. gambiae complex and A. stephensi and to calculate the inversion distances between ingroup and outgroup species. 2. To sequence and characterize the inversion breakpoints of Xc in A. arabiensis, Xa+, Xc+ in A. quadriannulatus, and 2Ro in A. merus, and the homologous sequences in A. stephensi. PUBLIC HEALTH RELEVANCE: This proposal will infer ancestral chromosome arrangements in the Anopheles gambiae complex. They are crucial in identifying the evolutionary genomic changes associated with the origin and loss of human blood choice, ecological and behavioral adaptations, and association with human habitats. These genomic changes should be targeted and manipulated so that malaria transmission can be reduced and eventually eliminated.

描述（由申请人提供）：冈比亚按蚊复合体的形态上难以区分的成员具有显著不同的生态适应、地理分布和行为。这种复合体包括主要的疟疾媒介（A. arabiensis、阿拉伯拟步行虫A. gambiae），以及次要媒介（A. bwamamarin，A. melas，黑刺山蚁A. merus）和非向量（A. quadriannulatus A，A. quadriannulatus B）。开发新的疟疾管理方法意味着找到用非病媒取代病媒种群的方法来阻断传播。我们目前对载体和非载体之间遗传组成差异的了解不足以实现成功的种群替换。推测A.冈比亚复合体在确定与人类血液选择的起源和丧失、生态和行为适应以及与人类栖息地的联系有关的进化变化方面至关重要。这些基因组变化应该是有针对性的和操纵的，以便减少并最终消除疟疾传播。尽管有可用的分子标记和基因组序列的A。冈比亚，成员之间的系统发育关系没有完全解决。由于复合体的起源较晚，高水平的序列相似性、遗传渐渗和共有的分子祖先多态性混淆了明确确定进化方向的能力。这个探索性的R21项目的主要目标是确定A.冈比亚情结。我们的方法的优点是，它是基于观察，祖先的安排之间共享的内组和外组物种和断点结构可以指示染色体进化的方向。我们计划（1）确定染色体排列之间共享的A。gambiae complex和外群种A. Stephensi和（2）确定倒位断点的衍生结构特征，例如转座/重复元件和基因复制的存在。内群和外群断点的比较分析将首次评估反转的独特性，并明确确定复杂的祖先X和2 R安排。虽然识别和测序断点是技术上具有挑战性的任务，2La断点的成功表征和我们的初步研究表明，我们的研究目标是可以实现的。我们的建议有两个具体目标：1。将固定倒位Xag、Xbcd、2 Rop的断裂点物理定位到A. gambiae complex和A. stephensi和计算内群和外群物种之间的倒置距离。2.对A. arabiensis，A. quadriannulatus和2 Ro。merus的同源序列，以及A.史蒂芬西公共卫生相关性：这项建议将推断冈比亚按蚊复合体的祖先染色体排列。它们在识别与人类血液选择的起源和丧失、生态和行为适应以及与人类栖息地的关联相关的进化基因组变化方面至关重要。这些基因组变化应该是有针对性的和操纵的，以便减少并最终消除疟疾传播。