Functional evolution of chromosomal inversions in Anopheles arabiensis

描述（申请人提供）：阿拉伯按蚊由于其高度的行为可塑性和适应不同环境条件的能力，已成为非洲最主要的疟疾媒介物种之一。这种强大的适应性与室内残留喷洒和驱虫蚊帐部署的有效性逐渐降低相平行。阿拉伯古猿的基因组已经通过多个多态性倒置进行了重新排列，其中一些被认为是该物种在大量环境条件下的扩张及其机会主义行为的工具。虽然在其姊妹物种冈比亚拟南芥中取得了显著的基因组学进展，但阿拉伯拟南芥却很少受到关注。在本研究中，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阿拉伯阿拉伯藜在局部适应湿度差异的背景下，两种广泛存在的染色体倒位（2Ra和3Ra）的作用。为此，我们将在布基纳法索对阿拉伯古猿种群进行抽样，在那里两种倒立都是自然分离的。此外，我们将首次使用高通量测序的成对末端读取（Illumina Solexa）来绘制这些反转的断点。在分子和计算水平上的常规程序将使我们能够表征断点区域，以阐明产生这两种反转的分子机制以及它们是否与位置效应有关。接下来，我们将通过使用新开发的阿拉伯阿拉伯芥微阵列平台研究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反转的替代染色体排列（倒立和共线）。我们将特别关注发育阶段（幼虫和成虫）和组织（尸体和头/天线）的不同染色体排列的表达差异，以破译由这两种倒置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pcr测定）来监测阿拉伯拟南芥自然种群的染色体排列，并将为新的基因组病媒控制措施发现新的候选基因。

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.