Functional evolution of chromosomal inversions in Anopheles arabiensis

描述（由申请人提供）：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。这种强大的适应性使室内滞留喷洒和使用驱虫蚊帐的效果逐渐降低。助理arabiensis基因组已经通过多个多态倒位进行了重排，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。虽然其姊妹种A. gambiae、A.阿拉伯人很少受到关注。在这项提案中，我们将使用一种新的采样策略和高通量基因组工具的组合，以解决两个广泛的染色体倒位（2 Ra和3Ra）在局部适应湿度差异的背景下的作用。阿拉伯的。为此，我们将抽样A。在布基纳法索，这两个倒位自然分离。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。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，以阐明起源于两个反转的分子机制以及它们是否与位置效应相关。接下来，我们将通过使用新开发的A.阿拉伯的。由此产生的功能分化的画像将使我们能够比较两种倒位的替代染色体排列（倒位和共线）。我们将特别注意表达分歧的替代染色体安排的发展阶段（幼虫和成人）和组织（尸体和头部/天线）破译的适应性反应，休息的选择和湿度适应介导的这两个倒置。重要的是，预期的结果将允许开发分子测试（例如PCR测定），用于监测自然种群中的染色体排列。并将为新的基因组病媒控制措施发现新的候选基因。 公共卫生相关性：染色体倒位多态性反复参与非洲主要疟疾媒介的休息偏好、摄食行为和栖息地范围的扩大，增加疟疾传播并降低媒介控制策略的有效性。利用完整的基因组序列和高通量分子技术的可用性，我们建议研究两个大陆广泛的倒位（2 Ra和3Ra），促进熟练的疟疾媒介阿拉伯按蚊适应湿度的差异。我们的研究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，并开发分子检测方法来监测不同环境参数季节变化背景下上述倒置的存在，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.