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）：冈比亚综合体的冈比亚综合体上不可分割的成员具有明显不同的生态适应，地理分布和行为。该复合物包括主要的疟疾载体（A. abiensis，a。gambiae），以及次要载体（A. Bwambae，A。Melas，A。Merus）和非向量（A. Quadriannulatus a，A。quadriannulatus b）。开发新型疟疾管理方法意味着通过用非向量代替向量人群来找到中断传播的方法。我们目前对向量和非向量之间基因组成差异的知识不足以实施成功的人群替代。冈比亚曲霉复合物中推断祖先的基因组特征对于确定与人类血液选择，生态和行为适应的起源和丧失以及与人类栖息地相关的进化变化至关重要。这些基因组变化应被靶向和操纵，以便可以减少疟疾的传播并最终消除。尽管分子标记物的可用性和冈比亚曲霉的基因组序列，但成员之间的系统发育关系并未完全解决。由于该复合物的最新起源，序列相似性的高水平，遗传渗入和共享的分子祖传多态性使人明确地确定进化方向的能力。该探索性R21项目的主要目的是确定冈比亚a. gambiae综合体中的祖先和衍生的染色体布置。我们方法的优点是基于观察结果，即祖先的排列是在群体和外部种类之间共享的，并且断点结构可以指示染色体进化的方向。我们计划（1）确定A. gambiae复合物与外群物种A. stephensi和（2）确定反转断点的衍生结构特征，例如存在转座/重复性元件和基因重复的存在。对组和外组断点的比较分析将首次评估反转的唯一性，并明确确定复合体中的祖先X和2R排列。尽管识别和测序断点是技术上具有挑战性的任务，但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。我们的提议有两个具体的目的：1。实际绘制固定反转XAG，​​XBCD，2ROP的断点到A. gambiae Complex和A. stephensi的染色体，并计算出群体和外部群体之间的倒数距离。 2。为了序列和表征Arabiensis，Xa+，Xc+在A. quadriannulatus中的XC的反转断点，而Merus中的2RO以及A. stephensi中的同源序列。公共卫生相关性：该提案将推断出冈比亚群岛综合体中的祖传染色体布置。它们对于确定与人类血液选择，生态和行为适应的起源和丧失以及与人类栖息地相关的进化基因组变化至关重要。这些基因组变化应被靶向和操纵，以便可以减少疟疾的传播并最终消除。