Functional evolution of chromosomal inversions in Anopheles arabiensis

描述(申请人提供)：由于其高度的行为可塑性和适应不同环境条件的能力，阿拉伯按蚊已成为非洲最主要的疟疾媒介物种之一。在这种强大的适应性的同时，室内滞留喷洒和部署驱虫蚊帐的效力也在逐步降低。阿拉比星的基因组通过多个多态倒置进行了重新排列，其中一些被认为有助于该物种在大量环境条件下的扩张及其机会主义行为。虽然冈比亚按蚊的基因组学研究取得了显著的进展，但阿拉伯按蚊却很少受到关注。在这项提案中，我们将使用采样策略和高通量基因组工具的新组合来解决两个广泛存在的染色体倒置(2ra和3ra)在阿拉比斯对湿度差异的局部适应背景下的作用。为此，我们将抽样布基纳法索的阿拉伯曲霉种群，在那里，两个倒位都是自然分离的。此外，我们将首次使用配对末端读取的高通量测序(Illumina Solexa)来映射这些倒置的断点。分子和计算水平的传统程序将使我们能够表征断点区域，以便阐明产生两个反转的分子机制，以及它们是否与位置效应有关。接下来，我们将使用一种新开发的阿拉伯曲线虫微阵列平台来研究这两种染色体排列的表达模式。由此产生的功能分化画像将使我们能够比较两种倒置的可选染色体排列(倒置和共线)。我们将特别关注发育阶段(幼虫和成虫)和组织(屠体和头/触角)的不同染色体排列中的表达差异，以破译这两个倒位介导的对休息选择和湿度适应的适应性反应。重要的是，预期的结果将允许开发分子测试(例如，聚合酶链式反应分析)，以监测自然种群的染色体排列，并将发现新的候选基因，用于新的基因组媒介控制措施。 与公共卫生相关：染色体倒置多态反复与非洲主要疟疾媒介的休息偏好、取食行为和栖息地范围扩大有关，增加了疟疾传播，并降低了媒介控制战略的有效性。利用全基因组序列和高通量分子技术，我们建议研究两个大陆广泛分布的倒位(2ra和3ra)，这两个倒位促进熟练的疟疾媒介阿拉伯按蚊对湿度差异的适应。我们的结果将有助于了解阿拉伯按蚊适应特定环境条件的遗传基础，并发展分子检测方法，在不同环境参数的季节性变化背景下监测上述倒置的存在，这将有助于设计更有效的控制策略。

DESCRIPTION (provided by applicant): Due to its high behavioral plasticity and capability to adapt to different environmental conditions, Anopheles arabiensis has become one of the most predominant malaria vector species in Africa. This formidable adaptability has paralleled a progressive reduction in the effectiveness of indoor residual spraying and deployment of insecticide-treated nets. The A. arabiensis genome has been rearranged by multiple polymorphic inversions, some of them considered to be instrumental in the expansion of this species across a large array of environmental conditions and in its opportunistic behavior. Although outstanding genomics advances have been achieved in its sister species A. gambiae, A. arabiensis has received little attention. In this proposal, we will use a novel combination of sampling strategies and high-throughput genomic tools to address the role of two widespread chromosomal inversions (2Ra and 3Ra) within the context of local adaptation to differences in humidity for A. arabiensis. For this purpose, we will sample A. arabiensis populations in Burkina Faso, where both inversions are naturally segregating. Further, we will use for the first time high-throughput sequencing of paired-ends reads (Illumina Solexa) to map the breakpoints of these inversions. Conventional procedures at the molecular and computational levels will allow us to characterize breakpoint regions in order to elucidate the molecular mechanisms that originated the two inversions and whether they are associated with position effects. Next, we will investigate the expression patterns across both chromosomal arrangements by using a newly developed microarray platform for A. arabiensis. The resulting portrait of functional differentiation will allow us to compare alternative chromosomal arrangements (inverted and collinear) for both inversions. We will pay special attention to expression divergence in alternative chromosomal arrangements for developmental stages (larva and adults) and tissues (carcasses and head/antenna) to decipher the adaptive response to resting choice and humidity adaptation mediated by these two inversions. Importantly, the expected outcomes will allow to develop molecular tests (e.g. PCR-assays) for monitoring chromosomal arrangements in natural populations of A. arabiensis and will uncover new candidate genes for new genomic vector control measures. PUBLIC HEALTH RELEVANCE: Chromosomal inversion polymorphism has been repeatedly involved in resting preference, feeding behavior and habitat range expansion of the major malaria vectors in Africa, increasing malaria transmission and reducing effectiveness on vector control strategies. Capitalizing on the availability of complete genome sequences and high-throughput molecular technologies, we propose to study two continent widespread inversions (2Ra and 3Ra) that facilitate the adaptation of the proficient malaria vector Anopheles arabiensis to differences in humidity. Our results will allow to understand the genetic basis of th adaptation of Anopheles arabiensis to particular environmental conditions and to develop molecular assays to monitor the presence of the mentioned inversions in the context of seasonal changes of different environmental parameters, which will help in the design of more effective control strategies.